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Background: Pulse oximeters are a non-invasive device useful in standardization of care in medical and dental offices for monitoring respiratory status during operative procedures. A close affiliation exists between the peripheral oxygen saturation (SpO2) and pulse rate which is affected by variables including exercise, traumatic events and operative procedures which may be encountered during standardized dental treatment. Aim: This study was carried out amongst 6-10-year-old children to evaluate the effect of dental operative procedures on peripheral oxygen saturation and pulse rate in Benin-City, Nigeria. Materials and methods: The peripheral oxygen saturation and pulse rate was assessed in 20 children each with a total number of 100 children. They were selected via a convenient sampling method for five procedures; 3 invasive (extraction, GIC filling and Pulpotomy) and 2 non-invasive (Fluoride therapy and scaling and polishing) procedures. The pulse oximeter was placed on the left index finger of each child at five different times: child in play room (PR1), child in the operatory (SR1), child on the dental chair before treatment (SR2), during treatment (SR3) and post treatment (PR2). The SpO2 level and pulse rate was then assessed at each time and recorded. Associations between frequencies were evaluated with the chi-square test. The Student’s t-test was used to compare means of the SpO2 and Pulse rate values. One way ANOVA was used for the values measured at different periods. Correlations between age, procedures and time were determined using the Statistical Package for Social Sciences (SPSS version 21) software. Significant values of P<0.05 were applied where applicable Results: The Mean age was 8.2 ± 0.7 years. There was a significant drop in the peripheral oxygen saturation (SpO2) levels for extractions and pulpotomy (mean range from 99% to 89% ± 1.6) respectively. Other procedures recorded a drop with a mean range from 99% to 96% ± 0.4 for GIC fillings and 99% to 94% ± 0.9 for scaling and polishing respectively during operative procedures (SR2). The SpO2 levels remained constant during topical fluoride therapy. The pulse rate increased sequentially for all procedures with its highest recorded value of 134bpm for scaling and polishing. There was also a significant increase in the pulse rate during operative dental procedures (SR2) for extractions, pulpotomies and scaling and polishing. Conclusion: Changes in SpO2 values occurred significantly during routine dental procedures in healthy young children with the critical values of less than 90% recorded during extractions and pulpotomies. | The study was conducted among 50 children in the age group of 8-9 yrs. to evaluate the anxiety producing dental procedures in the dental operatory viz. waiting at the reception area, examination in the dental chairs, scaling, polishing, cavity cutting, injection, extraction and post extraction period. The pulse rates were very high during local anaesthesia, extraction, waiting at reception and examination. A significant correlation was observed between the pulse rate and blood pressure. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,700 |
Radiofrequency (RF) lesions adjacent to the dorsal root ganglion (DRG) are increasingly used in the treatment of intractable chronic pain of spinal origin. Opinions differ on which nerve fibres are affected by these lesions. Morphological studies have been carried out to assess the effects of radiofrequency lesions on nervous tissue. Interpretation has been difficult, since most studies have been performed under circumstances which are not comparable to the clinical situation. This study was undertaken to investigate morphological effects of RF lesions as they develop in the normal clinical situation. In two goats 22 G 100 mm SMK electrodes with a 5 mm active tip (Radionics) were positioned posterior to the lumber dorsal root ganglia (DRG). Sixty-second 67C lesions were made on one side. The contralateral side was used as sham operation. The goats were sacrificed 2 weeks after the procedure. The lesions were studied for size as well as for effects on proliferation and regeneration using Ki-67 (MIB-1). Lesions made inside the DRG (23) were 1.8–2.0 mm in size. In these lesions there was a total loss of myelinated fibres. In lesions made adjacent to the DRG there was a significantly higher MIB-1 labelling on the treated side as compared to the sham-treated side. An RF lesion inside the DRG destroys myelinated fibres. A lesion adjacent to the DRG increases MIB-1 activity, indicating proliferation and regeneration after 2 weeks, despite the fact that the lesion was made outside the ganglion. | BACKGROUND/AIM ::: We investigated the short- and medium-term effectiveness of genicular nerve radiofrequency (RF) applied in patients with chronic knee pain due to osteoarthritis. ::: ::: ::: MATERIALS AND METHODS ::: Radiofrequency was performed in 49 patients with a diagnosis of knee osteoarthritis. VAS and WOMAC were measured at baseline and at 1, 4, and 12 weeks postprocedure. Under fluoroscopic guidance, the cannula was advanced percutaneously towards the area connecting the shaft to the epicondyle. The RF electrode was inserted through the cannula and the electrode tip temperature was raised to 80 °C for 90 s. One RF lesion was made for each genicular nerve. ::: ::: ::: RESULTS ::: Mean patient age was 64 ± 10.6. VAS score before the procedures was 8.9 ± 0.8, while 1, 4, and 12 weeks after the procedure it was 4.73 ± 3.23, 3.89 ± 2.9, and 3.93 ± 2.95, respectively. WOMAC score before the procedures was 64.26 ± 7.29, while 1, 4, and 12 weeks after the procedures it was 44.93 ± 13.18, 42.81 ± 13.15, and 43.04 ± 13.36, respectively. ::: ::: ::: CONCLUSION ::: RF neurotomy of genicular nerves led to significant pain reduction and functional improvement in a subset of elderly patients with chronic knee osteoarthritis pain, and thus may be an effective treatment in such cases. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,701 |
OBJECTIVE ::: To measure, and seek clinical correlates with, levels of substance P (SP) in the cerebrospinal fluid (CSF) of fibromyalgia syndrome (FMS) patients. ::: ::: ::: METHODS ::: CSF from 32 FMS patients and 30 normal control subjects was tested for SP by radioimmunoassay. Clinical measures included tender point examination and standardized questionnaires. ::: ::: ::: RESULTS ::: CSF SP levels were 3-fold higher in FMS patients than in normal controls (P < 0.001), but they correlated only weakly with tenderness found on examination. ::: ::: ::: CONCLUSION ::: SP is significantly elevated in FMS CSF, but other abnormalities must exist in FMS to more fully explain the symptoms. | TO THE EDITOR: An 87-year-old man was referred to the hospital for dysuria. His medical history consisted of mild dementia and recurrent urinary tract infections. On examination, vital signs were normal and the patient did not seem to be in distress. His sclera were mildly icteric, and central cyanosis was observed. Deep lemon-yellow discoloration of all nails was also noted. Other than an enlarged prostate, findings on physical examination were unremarkable. Laboratory tests revealed macrocytic anemia (hemoglobin level, 11.9 g/dL; mean corpuscular volume, 99 fL), a bilirubin level of 104 mol/L (mostly unconjugated), a lactate dehydrogenase level of 1063 U, a haptoglobin level of 11 mg/dL, and a creatinine level of 275 mol/L. At room air, arterial Po 2 was 92 mm Hg. These findings led to the suspicion of methemoglobinemia, which was confirmed by a methemoglobin level of 12.2%. The urine was orange and contained pus. On further questioning, the patient's son discovered that his father had been taking phenazopyridine, 300 mg/d, for more than 3 years. Therapy with the drug was discontinued, and the bilirubin level decreased. The patient left the hospital against medical advice 24 hours after admission. Further testing and follow-up were not possible. Phenazopyridine was recently reported as a cause of chronic intravascular hemolysis when taken at high doses [1, 2]. This drug also causes acute methemoglobinemia after intentional overdoses [3, 4] and causes altered skin pigmentation [5], both in association with renal failure. To our knowledge, yellow discoloration of the nails induced by phenazopyridine has not been reported. As in previous reports of phenazopyridine and altered skin pigmentation, the striking nail color contrasted with the mild scleral icterus and could not be explained by the mild hyperbilirubinemia. Long-term use and the toxic manifestations of this commonly prescribed drug are increasingly being recognized. The presence of intravascular hemolysis, methemoglobinemia, and abnormal pigmentation, alone or in combination, should raise the suspicion of phenazopyridine toxicity. In patients with renal failure, these side effects may be as pronounced at lower doses. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,702 |
Amlodipine (a new class of calcium channel antagonist) has been shown to limit the progression of arteriosclerosis and decrease the incidence of cardiovascular events. The mechanisms underlying the beneficial effects of amlodipine, however, remain unclear. Therefore, we hypothesized that amlodipine attenuates the development of arteriosclerosis through the inhibition of inflammation in vivo. Long-term inhibition of nitric oxide (NO) by administration of a NO synthase inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME), to rats induces coronary vascular inflammation [monocyte infiltration, monocyte chemoattractant protein-1 (MCP-1) expression, increased activity of angiotensin-converting enzyme (ACE)], and arteriosclerosis. Here, we used the rat model to investigate the anti-inflammatory effects of amlodipine in vivo. Treatment with amlodipine markedly inhibited the l-NAME-induced increase in vascular inflammation, oxidative stress, and local ACE and Rho activity and prevented arteriosclerosis. Interestin... | Objective Lacidipine has already been demonstrated to reduce the expression of some adhesion molecules induced by pro-oxidant signals on endothelial cells. In order to verify if this effect is a peculiarity of this molecule, or belongs to other dihydropyridinic compounds (DHPs), the activity of lacidipine was compared with that of lercanidipine, amlodipine, nimodipine and nifedipine. Design and methods The compounds were incorporated in human umbilical vein endothelial cells (HUVECs) using native low-density lipoprotein as a carrier. The drug concentrations in HUVECs were measured by mass spectrometry. Human recombinant tumour necrosis factors was then incubated with HUVECs for 7 h at 37°C for adhesion molecule expression. Results The cellular amount of lacidipine, lercanidipine and amlodipine was similar, while nimodipine and nifedipine were almost undetectable or undetectable, respectively. Lacidipine, at any concentration, determined a dose-dependent significant decrease of the expression of intercellular adhesion molecule-1 (ICAM-1) ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) VCAM-1 and E-selectin (P< 0.01). Lercanidipine and amlodipine determined variable decreases of adhesion molecules at the intermediate and highest concentrations. Nimodipine and nifedipine determined no effect on ICAM-1, VCAM-1 and E-selectin. The lowest IC 50 , i.e. the concentration determining the 50% reduction of ICAM-1, VCAM-1 and E-selectin expression was obtained with lacidipine for all the adhesion molecules considered (P < 0.01). Conclusions It is concluded that the effect of the DHPs used in this study on adhesion molecule expression is determined first by their lipophilicity and then by their intrinsic antioxidant activity. | The synthetic imidazoline-ammonium-salt corrosion inhibitor was compounded with sodium sulfite, isopropanol and potassium pyroantimonate respectively. Potassium pyroantimonate was selected as the best compound with good synergy. And the ratio of potassium pyroantimonate and the corrosion inhibitor was 3:50. Compared to the imidazoline corrosion inhibitor separately used, the inhibition efficiency was improved about 1.2% when the amount of the potassium pyroantimonate was 0.03%. Through researching the synergistic effect with polyaspartic acid, the green and high-efficient corrosion and scale inhibitor is got which is applicable to oilfield. | eng_Latn | 22,703 |
OBJECT ::: Non-small cell lung carcinomas with spinal and brachial plexus involvement have traditionally been considered to be Stage IIIb lesions and therefore unresectable. Advances in spinal surgery, the application of magnetic resonance (MR) imaging, and improvements in neoadjuvant therapy require a reassessment of the potential for complete resection. ::: ::: ::: METHODS ::: The authors conducted a retrospective review of all procedures involving the resection of superior sulcus tumors with spinal or brachial plexus involvement performed between 1985 and 1999. Assessment or resectability and operative planning were based on an MR imaging classification scheme in which the extent of spinal involvement was considered. Class A tumors involved the periosteum of the vertebral body (VB) (16 patients); Class B, distal neural foramen without epidural compression (eight patients); Class C, proximal neural foramen with epidural compression (four patients); and Class D, bone involvement (VB or posterior elements) with or without epidural involvement (14 patients). Brachial plexus involvement was present in 21 patients, including 17 with T-1 nerve root only and four with C-8 or lower-trunk infiltration. Complete tumor resection was achieved in 27 patients and incomplete resection in 15. Complications occurred in 14 patients, two of which were related to instrumentation failures. The overall median survival was 1.44 years. The median survival for the complete and incomplete resection groups were 2.84 and 0.79 years, respectively (p = 0.0001). There was no statistical difference in survival among classification groups. ::: ::: ::: CONCLUSIONS ::: Complete tumor resection of superior sulcus tumors is possible in selected patients in whom involvement of the spinal column and/or brachial plexus is present. Preoperative MR imaging is essential for evaluation of the spine and surgical planning. Survival and cure are dependent on complete resection, regardless of the extent of spinal involvement. | This review presents the options and limitations of MRI in non-vascular diseases of the mediastinum and the chest wall. In numerous thoracic pathologies, MRI is a useful supplement to spiral CT. This imaging procedure also allows a contrast-media-free differentiation of solid tumors and vascular lesions (e. g., aortic aneurysms). The advantages of MRI over CT are particularly useful when multiplanar tumor imaging is required prior to surgery to establish the exact spatial relationship between tumor and the other mediastinal structures. Primary indications for MRI in diseases of the mediastinum and chest wall are therefore: (a) tumors of the posterior mediastinum for determining their position in relation to the neural foramina and the spinal canal; (b) chest wall tumors; (c) preoperative multiplanar imaging of primary mediastinal tumors; and (d) contraindications against CT exams with iodine contrast media. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,704 |
Hydrogen sulfide (H2S) prevents endothelial cells damage and P-selectin of platelets promotes neutrophils extracellular traps (NETs) formation. However, how sodium hydrosulfide (NaHS), a donor that produces H2S regulates the activation of platelets and whether H2S inhibits the formation of neutrophils extracellular traps in hyperhomocysteinemia rats have not been previously investigated. The morphological and ultrastructural alterations of endothelial cells (ECs) and platelets were tested by transmission electron microscopy. The expressions of P-selectin of platelets were determined by flow cytometry. Additionally, the cellular ROS and the H2S level were detected by DCFH-DA staining and H2S probe, the expressions of Bax and Bcl-2 in arteries and cultured ECs from rat thoracic aortas and the phosphor-p38 mitogen-activated protein kinase (MAPK), CSE and CBS of platelets were measured by western blotting. The NETs formations, the concentration of DNA in serum and supernatant of cultured neutrophils stimulated with platelet-rich plasma (PRP) were tested by Sytox Green and PicoGreen commercial Kits. The vascular ECs damaged, the expression of P-selectin of platelets and NETs formation increased; the concentration of DNA in serum and supernatant of cultured neutrophils stimulated with PRP also increased; the expression of Bax increased while Bcl-2 decreased in arteries, the phosphor-p38 MAPK of platelets increased while CSE and CBS have no statistically significant changes in the HHcy group compared to the control group. In the cultured ECs, the ROS level increased while the H2S level decreased after 48 and 72 h treatment by HHcy; the expression of Bcl-2 decreased while Bax increased after 72 h treatment by HHcy. NaHS significantly inhibited the ECs injured, cellular ROS production, platelet activation and NETs formation, reversed the expressions of Bax, Bcl-2, phosphor-p38 MAPK, P-selectin and the increased concentration of DNA in serum and supernatant of cultured neutrophils which caused by high homocysteine. Our results demonstrate that the donor of H2S inhibits the platelets activation and NETs formation, which concerts the protection of ECs in hyperhomocysteinemia. | Cardiovascular disease is the main cause of death worldwide, but its pathogenesis is not yet clear. Hydrogen sulfide (H2S) is considered to be the third most important endogenous gasotransmitter in the organism after carbon monoxide and nitric oxide. It can be synthesized in mammalian tissues and can freely cross the cell membrane and exert many biological effects in various systems including cardiovascular system. More and more recent studies have supported the protective effects of endogenous H2S and exogenous H2S-releasing compounds (such as NaHS, Na2S, and GYY4137) in cardiovascular diseases, such as cardiac hypertrophy, heart failure, ischemia/reperfusion injury, and atherosclerosis. Here, we provided an up-to-date overview of the mechanistic actions of H2S as well as the therapeutic potential of various classes of H2S donors in treating cardiovascular diseases. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,705 |
The absolute rate of collagen synthesis by cultured bovine retinal capillary pericytes, determined using the specific radioactivity of proline in the cellular amino acid pool, was compared in media containing different concentrations of glucose (5, 10 or 40 m m ) and Sorbinil (0·0 or 0·1 m M ), an inhibitor of aldose reductase. The absolute rate of collagen synthesis, in proline molar terms, by pericytes in medium with 5 m m glucose was 3·3 ± 1·9 ( s.d. ) pmol 10 −7 cells 24 hr −1 , and increased significantly to 8·8 ± 3·7 pmol 10 −7 cells 24 hr −1 when the glucose concentration was increased to 40 m m . Sorbinil (0·1 m m ) reduced the elevated sorbitol contents of pericytes induced by high concentrations of glucose, but did not significantly change the absolute rate of collagen synthesis per cell. | As a consequence of an increased flux through the sorbitol pathway fructose levels rise in various tissues in diabetes. Also, in vitro nonenzymatic fructosylation of protein induces the generation of fluorescence at a rate 10 times greater than glucosylation. The administration of sorbinil, an aldose reductase inhibitor known to lower tissue fructose concentration, to experimental diabetic rats led to a decrease in the fluorescence related to advanced Maillard products in their skin collagen. This effect is consistent with the in vivo occurrence of nonenzymatic fructosylation of collagen. A potential pathogenetic role for this posttranslational modification in diabetic complications should be considered. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,706 |
BACKGROUND & AIMS ::: There is increasing need for accurate assessment of liver fibrosis/cirrhosis. We aimed to develop qFibrosis, a fully-automated assessment method combining quantification of histopathological architectural features, to address unmet needs in core biopsy evaluation of fibrosis in chronic hepatitis B (CHB) patients. ::: ::: ::: METHODS ::: qFibrosis was established as a combined index based on 87 parameters of architectural features. Images acquired from 25 Thioacetamide-treated rat samples and 162 CHB core biopsies were used to train and test qFibrosis and to demonstrate its reproducibility. qFibrosis scoring was analyzed employing Metavir and Ishak fibrosis staging as standard references, and collagen proportionate area (CPA) measurement for comparison. ::: ::: ::: RESULTS ::: qFibrosis faithfully and reliably recapitulates Metavir fibrosis scores, as it can identify differences between all stages in both animal samples (p<0.001) and human biopsies (p<0.05). It is robust to sampling size, allowing for discrimination of different stages in samples of different sizes (area under the curve (AUC): 0.93-0.99 for animal samples: 1-16 mm(2); AUC: 0.84-0.97 for biopsies: 10-44 mm in length). qFibrosis can significantly predict staging underestimation in suboptimal biopsies (<15 mm) and under- and over-scoring by different pathologists (p<0.001). qFibrosis can also differentiate between Ishak stages 5 and 6 (AUC: 0.73, p=0.008), suggesting the possibility of monitoring intra-stage cirrhosis changes. Best of all, qFibrosis demonstrates superior performance to CPA on all counts. ::: ::: ::: CONCLUSIONS ::: qFibrosis can improve fibrosis scoring accuracy and throughput, thus allowing for reproducible and reliable analysis of efficacies of anti-fibrotic therapies in clinical research and practice. | Fibrosis, a common pathogenic pathway of chronic liver disease (CLD), has long been indicated to be significantly and most importantly associated with severe prognosis. Nowadays, with remarkable advances in understanding and/or treatment of major CLDs such as hepatitis C, B, and nonalcoholic fatty liver disease, there is an unprecedented requirement for the diagnosis and assessment of liver fibrosis or cirrhosis in various clinical settings. Among the available approaches, liver biopsy remains the one which possibly provides the most direct and reliable information regarding fibrosis patterns and changes in the parenchyma at different clinical stages and with different etiologies. Thus, many endeavors have been undertaken for developing methodologies based on the strategy of quantitation for the invasive assessment. Here, we analyze the impact of fibrosis assessment on the CLD patient care based on the data of recent clinical studies. We discuss and update the current invasive tools regarding their technological features and potentials for the particular clinical applications. Furthermore, we propose the potential resolutions with application of quantitative invasive tools for some major issues in fibrosis assessment, which appear to be obstacles against the nowadays rapid progress in CLD medicine. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,707 |
Background In pre-clinical models enhanced anti-tumour activity was observed when SU-014813, an oral multi-targeted tyrosine kinase inhibitor was combined with docetaxel. This synergy might be explained by improvement of the penetration of cytotoxic agents into tumours as a result of both VEGFR and PDGFR inhibition. We assessed the maximal tolerated dose (MTD), evaluated the pharmacokinetics and preliminary anti-tumour efficacy of oral SU-014813 administered continuously in combination with docetaxel to patients with advanced solid tumours. Methods In this phase I study successive patient cohorts received docetaxel 60 or 75 mg/m 2 every 3 weeks in combination with chronic daily dosing of SU-014813. Dose limiting toxicity was assessed both in the first and second treatment cycle. Results Twenty-five patients were entered on study of which 24 started treatment. Dose limiting toxicities were prolonged neutropenia, neutropenic fever, fatigue and diarrhoea. Other toxicities included fatigue, alopecia, nausea, vomiting, anorexia, rash, hypertension and hair discolouration. The recommended phase II dose was determined to be docetaxel 75 mg/m 2 in combination with SU-014813 50 mg/day. There was no clinically relevant pharmacokinetic drug–drug interaction. Two patients (8%) achieved a partial response (PR) and 7 patients (29%) had stabilisation of their disease (SD) >6 months, for a clinical benefit rate of 37.5%. The activity observed in patients with melanoma and sunitinib refractory gastrointestinal stromal tumours (GIST) was particularly noteworthy. Conclusions Oral SU-014813 50 mg/day with docetaxel 75 mg/m 2 is a clinically feasible regimen with a manageable safety profile and anti-tumour activity. Further development is warranted in patients with melanoma and GIST. | Commentary on: ::: ::: [Shem Patyna, A. Douglas Laird, Dirk B. Mendel, Anne-Marie O'Farrell, Chris Liang, Huiping Guan, Tomas Vojkovsky, Stefan Vasile, Xueyan Wang, Jeffrey Chen, Maren Grazzini, Cheng Y. Yang, Joshua O. Haznedar, Juthamas Sukbuntherng, Wei-Zhu Zhong, Julie M. Cherrington, and Dana Hu- | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,708 |
The aim of the present work was to investigate the impact of disease states and environmental and host factors on the glucuronidation of oxazepam. Glucuronidation represents quantitatively one of the most important metabolic conjugation pathways (phase II) in man for the inactivation and detoxication of xenobiotics and endogenous compounds and the liver is the major site for it to take place. Far less attention has been paid to the conjugation reactions in previous clinical research in this field compared to the immense interest in the oxidative biotransformation pathways (phase I). This fact is mainly due to the latter giving rise to active or reactive metabolites with a toxicological potential. The metabolism of oxazepam expresses exclusively the capacity for glucuronide formation. It was a prerequisite to establish the bioavailability of oxazepam prior to succeeding studies on the oral disposition of the drug. A preparation for intravenous administration was created. Clearance was chosen as measurement of the capacity to glucuronidate oxazepam. Severe decompensated liver disease was associated with a significant decrease in oxazepam clearance, that became even more obvious when corrected for by a diminished binding to plasma proteins. This increase in free fraction of oxazepam was substantial and could mainly be accounted for by low plasma albumin values. The results are in part a settlement with earlier studies on glucuronidation in liver disease and they may undoubtedly be ascribed to the severe degree of liver disease. For the first time it was shown that hypothyroidism led to a decline in the clearance and metabolism of oxazepam and paracetamol that is mainly biotransformed by glucuronidation. It was concluded that the enzymes responsible for glucuronidation in hypothyroidism are under the influence of thyroid hormones as is the case with oxidative enzymes. Further studies focused on the effect of host and environmental factors on glucuronidation. A commercially available very low calorie product for the treatment of obesity resulted in a decrease in oxazepam clearance and a lack of co-factors as a consequence of the low calorie intake was explanatorily proposed. Beta-adrenoceptor antagonists are often prescribed together with other drugs and close knowledge on interactions is mandatory but insufficient in regard of drugs being glucuronidated. Despite the mutual metabolic pathway labetalol exerted no dispositional alterations concerning oxazepam. It was moreover suggested that very elderly subjects between the age of 80 to 94 years had a reduced clearance of oxazepam.(ABSTRACT TRUNCATED AT 400 WORDS) | The phase I cytochrome P450 (CYP) isoenzymes have received substantial attention in the pharmacogenetic literature. Researchers are beginning to examine the role of the phase II UDP-glucuronosyltransferase (UGT) enzymes, which produce products that are more water-soluble, less toxic and more readily excreted than the parent compounds. Several reasons may have contributed to neglect of UGTs (compared to CYPs) including: (1) the overlapping activity of UGTs and lack of selective probes; (2) the complexity of the glucuronidation cycle; and (3) the difficulty in developing analytic methods to measure glucuronides. Current CYP knowledge is used as a model to predict advances in UGT knowledge. At least 24 different UGT human genes have been identified and are classified in two families (UGT1 and UGT2) based on sequence homology. The UGT1A subfamily (genes located on chromosome 2) glucuronidates bilirubin, thyroid hormones, and some medications. UGT1A4 metabolizes tricyclic antidepressants and some antipsychotics. The UGT2B subfamily (genes located on chromosome 6) glucuronidates sexual steroids and bile acids. Oxazepam and lorazepam are mainly metabolized by glucuronidation. Anti-epileptics with mood-stabilizing properties are frequently metabolized by UGTs. Opioid and nicotine addiction may also be influenced by glucuronidation. Glucuronidation of serotonin may be important during fetal development. UGTs appear to be in small concentrations in brain tissue (and higher concentrations at brain capillaries). However, UGTs may be localized in certain brain areas to provide a neuroprotective function. This review illustrates the importance of glucuronidation and the implications for psychiatry. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,709 |
Wild-type or equipotent variants of recombinant staphylokinase (rSak) were given intra-arterially (as a 2 mg bolus injection followed by an infusion of 1 mg/h or 0.5 mg/h overnight, with concomitant heparin [1000 IU/h]) to 191 patients of less than 80 years (62 ± 1 years, mean ± SEM), with a peripheral arterial occlusion (PAO) of less than 120 days (mean 14 ± 1 days, median 11 days, 5 to 95 percentiles 3 to 30 days). Ninety nine patients presented with acute or subacute ischemia, 57 with severe claudication, 33 with chronic rest pain and 2 with gangrene. Occlusion occurred in 122 native arteries and in 69 grafts. Revascularization was complete in 83 percent (158/191), partial in 13 percent (24/191) and absent in 4 percent (7/191) after administration of 12 ± 0.5 mg rSak over 14 ± 0.7 h. Complete revascularization of acute occlusions of popliteal or more distal arteries was less frequent (60 percent, 15/25) than of acute occlusions of more proximal native arteries (95 percent, 37/39, p 0.001) or grafts (89 percent, 50/56, p = 0.005). Additional endovascular procedures were performed in 47 percent and subsequent elective bypass surgery in 23 percent of patients. Major bleeding occurred in 12 percent (23/191), one month mortality was 3.1 percent (6/191) and one year mortality was 6.9 percent (12/174). However, four patients (2.1 percent) had an intracranial bleeding following therapy: a 85 year old woman with severe diabetic arteriopathy, who was included in violation of the protocol, a 79 and a 74-year-old woman and a 74-year-old man, all with severe hypertension and limb threatening ischemia; these four patients died within two months after treatment. Amputations were performed within the first year in 16 of 162 surviving patients (9.8 percent): in 7 percent (7/96) with an occluded native artery and 14 percent (9/66) with an occluded graft (p = 0.19). No significant difference in lysis rate, one month mortality or one year amputation-free survival was observed in occlusions of recent onset (14 days, n = 126) as compared to occlusions of longer duration (14 days, n = 65). Treatment was interrupted prematurely in 4 patients because of a suspected allergic reaction. Fibrinogen levels remained unaffected during treatment (3.3 ± 0.1 g/l before vs. 3.3 ± 0.1 g/l after infusion, n = 167). | In an effort to combine the benefits of fibrinolytics, such as staphylokinase, with those of thrombin inhibitors for the prevention of vessel reocclusion after vascular injury, we have produced several chimeric proteins with plasminogen-activating and thrombin-inhibiting properties. Fusion proteins were constructed consisting of the modules staphylokinase (Sak), the factor Xa cleavage site, and various dipetalin (Dip) domains (H(6)-Sak-Dip-I+II, H(6)-Sak-Dip-I, and H(6)-Sak-Dip-II). Sak stimulates fibrinolysis via activation of plasminogen, whereas dipetalin is a two-domain, Kazal-type inhibitor of thrombin. NMR spectroscopy of the fusion proteins revealed that the molecular structures of the modules are retained in the fusion protein and that no significant interactions occur between the modules in terms of their functionally relevant regions. In enzymatic thrombin inhibition tests and blood coagulation assays (thrombin, prothrombin, and activated partial thromboplastin times), no significant differences in anticoagulant capacity were observed between the fusion protein H(6)-Sak-Dip-I+II and isolated Dip-I+II, even at nanomolar concentrations. Similar results (i.e., the inhibition of thrombin-induced platelet aggregation and the inhibition of thrombin-induced vascular relaxation) were obtained when the cellular thrombin effects were studied. The fusion protein containing Dip-I has less but still significant thrombin inhibitory effects compared with those of H(6)-Sak-Dip-I+II. In contrast, the H(6)-Sak-Dip-II protein failed to inhibit thrombin in each of the assays used. The plasminogen-activating and fibrinolytic activities of the fusion proteins are similar to those of wild-type Sak. The individual dipetalin domains do not activate plasminogen. In conclusion, the fusion protein H(6)-Sak-Dip-I+II is a bifunctional molecule able to activate fibrinolysis via plasminogen activation and inhibit blood coagulation via direct inhibition of thrombin. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,710 |
Objectives To investigate construct validity and responsiveness of the novel ankylosing spondylitis (AS) disease activity score (ASDAS) in patients with spondyloarthritis (SpA). Methods In a 46-week prospective longitudinal multicentre study of 60 patients with SpA (80% men, median age 40 years (range 21–62)) treated with tumour necrosis factor α (TNFα) inhibitors (infliximab, n=41; etanercept, n=13; adalimumab, n=6), the responsiveness of ASDAS, conventional clinical measures of disease activity and treatment response and the Berlin MRI sacroiliac joint (SIJ) and lumbar spine inflammation scores were compared. Results After 22 weeks, 58.3% of the patients were clinical responders (50% or 20 mm reduction in the Bath AS Disease Activity Index (BASDAI)). At baseline, clinical responders had significantly higher median (range) ASDAS than non-responders (4.15 (1.98–6.04) vs 2.99 (2.05–6.19), p=0.008). Changes in ASDAS correlated with changes in clinical measures of disease activity (including BASDAI (ρ=0.76) and C-reactive protein (CRP) (0.79)), MRI SIJ inflammation (0.46) and MRI total inflammation scores (0.34). Patients with higher BASDAI or Assessment of SpondyloArthritis International Society (ASAS) responses obtained more profound reductions in ASDAS. ASDAS had the highest responsiveness with an effect size of 2.04 and a standardised response mean of 1.45, whereas BASDAI (effect size 1.86; standardised response mean 1.36) and CRP (effect size 0.63; standardised response mean 0.70) were less responsive. Linear regression showed that a change in BASDAI of 20 mm or 50% corresponded to a change in ASDAS of 1.38 and 1.95, respectively. Conclusion ASDAS demonstrates construct validity and high responsiveness during treatment with TNFα inhibitors in patients with SpA. The proposed thresholds for disease activity and treatment response need further validation. Trial registration number NCT00133315. | AIM ::: To establish guidelines for the clinical management of axial spondyloarthritis that take into account local issues and clinical practice concerns for Taiwan. ::: ::: ::: METHOD ::: Overarching principles and recommendations were established by consensus among a panel of rheumatology and rehabilitation experts, based on analysis of the most up-to-date clinical evidence and the clinical experience of panelists. All Overarching Principles and Recommendations were graded according to the standards developed by the Oxford Centre for Evidence Based Medicine, and further evaluated and modified using the Delphi method. ::: ::: ::: RESULTS ::: The guidelines specifically address issues such as local medical considerations, National Health Insurance reimbursement, and management of extra-articular manifestations. ::: ::: ::: CONCLUSION ::: It is hoped that this will help to optimize clinical management outcomes for axial spondyloarthritis in Taiwan. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,711 |
According to the theory of traditional Chinese medicine, cerebral infarction results from blood stasis, and the method of quickening the blood and dispelling stasis is used to treat cerebral infarct. Salvia Miltorrhiza Bunge (SM) is a Chinese herb, which is considered to have an action of quickening the blood and dispelling stasis, and is frequently used to treat related disorders of blood stasis such as cerebrovascular accident and ischemic heart disease. The aim of the present study was to investigate the effect of SM on cerebral infarct in ischemia-reperfusion injured rats. A total of 30 Sprague-Dawley (SD) rats were studied. A model of focal cerebral infarct was developed by occluding both common carotid arteries and the right middle cerebral artery for 90 minutes. After 24 hours reperfusion, the rats were killed and the brain tissue was stained with 2, 3, 5-triphenyl-tetrazolium chloride (TTC). The areas of cerebral infarct were calculated, and lumino-chemiluminesence (CL) counts and lucigenin-CL counts of peripheral blood taken at this time were measured. The changes in the area of cerebral infarct were used as an index to evaluate the effect of SM on cerebral infarct. The results indicated that pretreatment with intraperitoneal injection of 30 mg/kg and 15 mg/kg SM reduced the area of cerebral infarct and also reduced the luminol-CL counts of peripheral blood in ischemia-reperfusion injured rats. This study has demonstrated that SM can reduce the area of cerebral infarct in ischemia-reperfusion injured rats, suggesting it may be useful in the treatment of cerebral infarct in humans. The therapeutic effect of SM may be partly due to its free radical scavenging activities. | Danshen, the dried root of Salvia miltiorrhiza, is a Chinese medicine used to promote blood flow and treat vascular disease. The present article reviews the pharmacological effects of Danshen on cerebral infarction and possible interactions between Danshen and Western drugs. Danshen may reduce or prolong the development of atherosclerosis and may have anti-hypertensive and anti-platelet aggregation effects, which prevent cerebral infarction. Danshen may enhance endogenous anti-oxidative enzyme activities such as the expression of endothelial nitric oxide synthase and may scavenge oxygen free radicals. Prevention and treatment of cerebral infarction by Danshen involves multiple pathways, including anti-atherosclerosis, anti-hypertension, anti-platelet aggregation, anti-inflammatory and anti-oxidative effects. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,712 |
BACKGROUND ::: Diabetic patients are at high risk to develop atherosclerotic cardiovascular disease and have a higher restenotic rate after percutaneous coronary intervention (PCI). Statins improve cardiovascular outcome and reduce restenosis after PCI by inhibiting proliferation and migration of vascular smooth muscle cells (VSMCs). But the effect of statins on diabetes without dyslipidemia was still not fully understood. Our previous study has demonstrated that simvastatin inhibits VSMC proliferation in high glucose status without dyslipidemia, inducing a G0/G1 phase cell cycle growth arrest by acting on multiple steps upstream of pRb, including inhibition of CDK2/4 expression and upregulation of p53, p21, p16, and p27. ::: ::: ::: METHOD ::: Following our previous study, we investigated the mechanism of simvastatin inhibition of VSMC migration in a diabetes-like model (A7r5 cells under high glucose conditions without dyslipidemia). ::: ::: ::: RESULTS ::: Under high glucose conditions, simvastatin dose-dependently inhibited VSMC migration, decreased PI3K/Akt pathway activity, reduced c-Raf and Ras expression, increased RhoB but not RhoA, Rac1, and Cdc2 expression, dose-dependently inhibited MMP-2, but not MMP-9, activity, and dose-dependently inhibited NF-κB activity. ::: ::: ::: CONCLUSION ::: The inhibition of VSMC migration under high glucose conditions was via two different pathways. The first pathway is mevalonate-related but not RhoA protein-related and involves suppression of Ras and PI3K/Akt signals. The second pathway is not mevalonate-related and involves increasing RhoB expression directly. | BACKGROUND ::: Cyclophilin A (CyPA), a cyclosporine A-binding protein, influences abdominal aortic aneurysm (AAA) formation and the ERK1/2 signalling pathway in animal and in vitro studies. Statins decrease CyPA in smooth muscle cells although their influence on CyPA in human AAA is unknown. ::: ::: ::: MATERIAL AND METHODS ::: The study was performed on AAA wall-tissue samples obtained from 30 simvastatin-treated and 15 non-statin patients (2:1 case to control). The patients were matched by age, sex and AAA diameter. We investigated the gene expression of CyPA, its receptor extracellular matrix metalloproteinase inducer (EMMPRIN) by real-time RT-PCR. CyPA and EMMPRIN protein level and phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) were measured by Western blot. ::: ::: ::: RESULTS ::: The AAA wall tissue from simvastatin-treated patients had significantly lower CyPA gene expression and protein levels (P = 0.0018, P = 0.0083, respectively). Furthermore, phosphorylation of ERK1 and ERK2 was markedly suppressed in the simvastatin group (P = 0.0002, P = 0.0027, respectively). However, simvastatin did not influence EMMPRIN gene and protein expression. ::: ::: ::: CONCLUSION ::: Simvastatin-treated patients with AAA exert lower CyPA messenger RNA (mRNA), as well as CyPA intracellular protein levels and a decreased amount of phospho-ERK1/2. Thus, the interference with signalling pathways leading to CyPA formation and ERK1/2 activation reveals a new anti-inflammatory role of statins in AAA. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,713 |
The intrinsic antioxidant capacities of the bile pigments biliverdin and bilirubin are increasingly recognized since both heme degradation products can exert beneficial cytoprotective effects due to their scavenging of oxygen free radicals and interaction with antioxidant vitamins. Several studies have been published on the localization of the carbon monoxide producing enzyme heme oxygenase-2 (HO-2), which concomitantly generates biliverdin; histochemical data on the distribution of biliverdin reductase (BVR), converting biliverdin to bilirubin, are still very scarce in large mammals including humans. The present study revealed by means of immunohistochemistry the presence of BVR and HO-2 in mucosal epithelial cells and in the endothelium of intramural vessels of both human and porcine gastric fundus. In addition, co-labeling with the specific neural marker protein-gene product 9.5 (PGP 9.5) demonstrated that both BVR and HO-2 were present in all intrinsic nerve cell bodies of both submucous and myenteric plexuses, while double labeling with c-Kit antibody confirmed their presence in intramuscular interstitial cells of Cajal (ICC). Our results substantiate the hypothesis that BVR, through the production of the potent antioxidant bilirubin, might be an essential component of normal physiologic gastrointestinal defense in man and pig. | Background ::: Although bilirubin has been generally regarded as a waste with potential neurotoxicity at high levels, a few clinical studies suggest a potential protective role of physiological serum total bilirubin (TBIL) concentrations in diabetic peripheral neuropathy (DPN). However, the pathological mechanisms underlying the relationship remain poorly understood. The objective of this study was to explore the relationship between serum TBIL and DPN, and clinical and laboratory parameters. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,714 |
Background and purpose ::: Studies on cognitive decline in myotonic dystrophy type 1 (DM1) are characterized by conflicting results. The purpose of the present study was to analyse possible decline in classical/adult onset DM1 at a 5-year follow-up and to explore the correlation with disease-related and demographic factors. ::: ::: Methods ::: Patients with DM1 (n = 37) were examined with a comprehensive neuropsychological test battery yielding measures on memory, attention, verbal, visuospatial and executive functions. Assessment of muscle impairment and CTG repeat expansion size was performed. ::: ::: Results ::: A majority of the participants (65%) performed worse at follow-up. Compared to normative data, patients scored significantly worse on tests measuring memory, attention, visuospatial construction and verbal ability. Neither CTG repeat size nor muscle impairment related to cognitive decline. However, age at onset and disease duration were correlated with the number of tests in which performance was below 1 SD at both baseline and follow-up examination. ::: ::: Conclusions ::: Measurements show that classical/adult onset DM1 is characterized by cognitive decline. Both earlier onset and longer duration of the disease are indicative of more cognitive deficits. | Myotonic dystrophy (DM) and facioscapulohumeral muscular dystrophy (FSHD) are the two most common adult muscular dystrophies and have progressive and often disabling manifestations. Higher levels of medication adherence lead to better health outcomes, especially important to patients with DM and FSHD because of their multisystem manifestations and complexity of care. However, medication adherence has not previously been studied in a large cohort of DM type 1 (DM1), DM type 2 (DM2), and FSHD patients. The purpose of our study was to survey medication adherence and disease manifestations in patients enrolled in the NIH-supported National DM and FSHD Registry. The study was completed by 110 DM1, 49 DM2, and 193 FSHD patients. Notable comorbidities were hypertension in FSHD (44 %) and DM2 (37 %), gastroesophageal reflux disease in DM1 (24 %) and DM2 (31 %) and arrhythmias (29 %) and thyroid disease (20 %) in DM1. Each group reported high levels of adherence based on regimen complexity, medication costs, health literacy, side effect profile, and their beliefs about treatment. Only dysphagia in DM1 was reported to significantly impact medication adherence. Approximately 35 % of study patients reported polypharmacy (taking 6 or more medications). Of the patients with polypharmacy, the DM1 cohort was significantly younger (mean 55.0 years) compared to DM2 (59.0 years) and FSHD (63.2 years), and had shorter disease duration (mean 26 years) compared to FSHD (26.8 years) and DM2 (34.8 years). Future research is needed to assess techniques to ease pill swallowing in DM1 and to monitor polypharmacy and potential drug interactions in DM and FSHD. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,715 |
Both insulin resistance and reactive oxygen species (ROS) have been reported to play essential pathophysiological roles in cardiovascular diseases. However, the mechanistic link between ROS and insulin resistance in the vasculature remains unclear. Recently we have shown that insulin causes KATP channel activation mediated by PI3K in cultured vascular smooth muscle cells (VSMCs). KATP channel in VSMCs is critical in the regulation of vascular tonus. Here we examined the effects of ROS induced by a thol-oxidizing agent, diamide, on the insulin signalling pathway and KATP channel activities in cultured VSMCs (A10 cells). Diamide (100 microM) increased intercellular ROS and extracellular signal-regulated kinases (ERK) activity. Treatment with 100 M diamide suppressed significantly insulin-induced IRS and Akt phosphorylation. In addition to IRS and Akt, diamide inhibited insulin receptor auto-phosphorylation. Patch-clamp study showed that diamide suppressed insulin-induced but did not pinacidil-induced KATP channel activities in A10 cells. From these data, we conclude that ROS inhibit critical insulin signal transduction components including IRS and Akt, and these effects cause down-regulation of insulin's action in the vasculature including KATP channel activation. This study may contribute to our understanding of mechanisms of insulin resistance-associated cardiovascular disease. | Reactive oxygen species (ROS) have been proposed to mediate vascular hypertrophy induced by angiotensin II (Ang II). Recently, we and others have shown that growth-promoting signals by Ang II involve protein tyrosine kinase (PTK) and extracellular signal-regulated kinase (ERK). However, whether ROS contribute to the Ang II-induced PTK and/or ERK activation in vascular smooth muscle cells (VSMCs) remains largely unclear. Here, we have investigated the possible involvement of ROS in Ang II-induced PTK and ERK activation. In the presence of a NADH/NADPH oxidase inhibitor, diphenyleneiodonium (DPI) or an antioxidant,α -tocopherol, Ang II-induced protein tyrosine phosphorylation of two major proteins (p120, p70) and ERK activation were markedly reduced, whereas ERK activation by epidermal growth factor was unaffected. DPI also inhibited Ang II-induced H2O2 production and PTK activation. In this regard, H2O2 and a membrane permeable thiol-oxidizing agent, diamide, stimulated protein tyrosine phosphorylation of ... | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,716 |
Renal fibrosis is a critical process underlying the development progression of chronic kidney disease to end-stage renal disease, which has intrigued much attention. This study aimed to investigate the role of Sphingosine kinase 1 (SphK1) on epithelial-mesenchymal transition (EMT) in renal fibrosis and the potential regulatory mechanisms. In the present study, unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis model was established. HE and Masson staining were employed to detect the pathological change and fibrous deposition in renal tissues respectively. Moreover, the expression of SphK1, EMT relative proteins including E-cadherin (E-cad), N-cadherin (N-cad) and vimentin as well as fibrosis marker protein α-smooth muscle actin (α-SMA) were measured by immunohistochemistry and Western blot, respectively. In vitro, SphK1 silencing was generated in TGF-β induced human renal tubular epithelial HK-2 cells. Immunofluorescence staining was applied to examine the expression of α-SMA, then the levels of EMT relative proteins and NF-κB signaling were measured using Western blot. The results revealed that notably tubulointerstitial damage and fibrous deposition were detected in the UUO mouse renal tissues. The expression level of E-cad and SphK1 were decreased coupled with an increase of N-cad, vimentin and α-SMA expression. Furthermore, after knockdown of SphK1 in TGF-β induced HK-2 cells, the E-cad expression was up-regulated while N-cad, vimentin and α-SMA expression were down-regulated remarkably. In addition, the expression levels of phospho-NF-κB p65 (p-NF-κB p65) and p-IκB-α were lowered significantly following SphK1 silencing. These findings indicated that the inhibition of SphK1 protected renal tubular epithelial cells against renal fibrosis, by contribution to decrease the EMT via blocking the NF-κB signaling. Therefore, SphK1 may serve as a therapeutic target in the future. | Surfactant proteins A and D (SP-A and SP-D) are lung collectins composed of two regions, a globular head domain that binds PAMPs and a collagenous tail domain that initiates phagocytosis. We provide evidence that SP-A and SP-D act in a dual manner, to enhance or suppress inflammatory mediator production depending on binding orientation. SP-A and SP-D bind SIRPα through their globular heads to initiate a signaling pathway that blocks proinflammatory mediator production. In contrast, their collagenous tails stimulate proinflammatory mediator production through binding to calreticulin/CD91. Together a model is implied in which SP-A and SP-D help maintain a non/anti-inflammatory lung environment by stimulating SIRPα on resident cells through their globular heads. However, interaction of these heads with PAMPs on foreign organisms or damaged cells and presentation of the collagenous tails in an aggregated state to calreticulin/CD91, stimulates phagocytosis and proinflammatory responses. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,717 |
Human platelets with a high content of endogenous serotonin took up more serotonin when incubated with exogenous serotonin, than platelets with a low endogenous content of serotonin. Also, thrombin-stimulated serotonin secretion (%) was high when endogenous serotonin was high. This was not found with fresh platelets, but was found when platelets were stored as platelet concentrates for 5 and 7 days. With platelets stored for 5 or 7 days, both uptake and secretion were increased after preincubation of the platelets with an amount of exogenous serotonin that was completely taken up. Inhibition of the reuptake of serotonin by imipramine during thrombin-induced secretion increased the secretion in stored platelets. Agonists like collagen, ADP, and a prostaglandin analogue (U46619) gave only 3-7% secretion. Imipramine increased the secretion induced by U46619, but not the secretion induced by ADP or collagen. The specific 5-HT(2) receptor inhibitor, ketanserin, had no effect on agonist stimulated secretion, or secretion stimulated by a calcium ionophore (A23187). Both the uptake and the thrombin-induced secretion of serotonin correlated significantly with endogenous serotonin in stored platelets. In fresh platelets the uptake of serotonin correlated positively, although not significantly, with endogenous serotonin. It is speculated that endogenous serotonin may affect secretion through stimulation of the thrombin receptor, at least in stored platelets. | Background ::: Trimetazidine is an anti-ischemic drug that can inhibit platelet aggregation and regulate serotonin (5-hydroxytryptamine [5-HT]) release. The purpose of this study was to investigate the therapeutic effects of trimetazidine on 5-HT and serotonin transporter (SERT) expression in experimentally induced myocardial infarction (MI), depression, and MI + depression. ::: ::: ::: Materials and methods ::: Eighty Sprague Dawley (SD) rats were randomly divided into a trimetazidine group and a saline group of 40 rats each. The trimetazidine group was given trimetazidine pretreatment for 4 weeks, while the saline group received saline for 4 weeks. Both groups were then subdivided into four subgroups (n=10), which were each subjected to a unique disease condition: sham surgery, MI, depression, or MI + depression. All rats were sacrificed 3 days thereafter, and serum and platelet levels of 5-HT and SERT were assessed. In addition, we experimented with trimetazidine posttreatment. Twenty SD rats underwent MI surgery, and were then randomly divided into a treatment and a saline group (n=10 each). For 4 weeks post-surgery, the trimetazidine group was given trimetazidine, while the saline group received saline. Serum and platelet levels of 5-HT and SERT were assessed. ::: ::: ::: Results ::: Pretreatment with trimetazidine: in the nontreatment saline group, MI, depression, and MI + depression showed significant declines (P<0.05) in both serum and platelet 5-HT levels compared to sham. Trimetazidine treatment significantly increased serum and platelet 5-HT levels in the MI, depression, and MI + depression (P<0.05) subgroups compared to their counterparts in the saline group. Results for SERT were heterogeneous between serum and platelets. Trimetazidine treatment significantly decreased serum levels of SERT in the sham surgery subgroup (P<0.05), while significantly increasing levels in depression rats, compared to control (P<0.05). In platelets, trimetazidine significantly decreased SERT in sham surgery, MI, depression, and MI + depression rats, compared to control (P<0.05). This contrast suggests that trimetazidine has opposite effects in serum and platelet SERT levels for the three disease models. Post-surgery trimetazidine: increased serum 5-HT (P<0.05) and serum SERT (P<0.05) were observed, compared to control. In platelets, trimetazidine decreased both 5-HT and SERT compared to control, significantly (P<0.05) for 5-HT, but not significantly for SERT (P>0.05). ::: ::: ::: Conclusion ::: Trimetazidine has a regulatory effect on 5-HT and SERT in the serum and platelets. Because of the downstream effects of this regulation on blood vessel function and myocardial protection, trimetazidine may be a therapeutic or preventive agent in several disease processes, including MI, depression, and the comorbidity between these two diseases. Further investigation, aimed at exploring the clinical potential of trimetazidine, is therefore warranted. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,718 |
1. The hypothesis that endogenous superoxide dismutase (SOD) protects the nitrergic transmitter from inactivation by superoxide and that this explains the lack of sensitivity of the transmitter to superoxide generators was tested in the rat isolated anococcygeus muscle. 2. Responses to nitrergic nerve stimulation or to NO were not significantly affected by exogenous SOD or by the Cu/Zn SOD inhibitor diethyldithiocarbamic acid (DETCA). 3. Hydroquinone produced a concentration-dependent reduction of responses to NO with an IC50 of 27 microM, and higher concentrations reduced relaxant responses to nitrergic nerve stimulation with an IC50 of 612 microM. The effects of hydroquinone were only slightly reversed by SOD, so it does not appear to be acting as a superoxide generator. 4. Pyrogallol produced a concentration-dependent reduction in responses to NO with an IC50 value of 39 microM and this effect was reversed by SOD (100-1000 u ml(-1)). Pyrogallol did not affect responses to nitrergic nerve stimulation. Treatment with DETCA did not alter the differentiating action of pyrogallol. 5. Duroquinone produced a concentration-dependent reduction of relaxations to NO with an IC50 value of 240 microM and 100 microM slightly decreased nitrergic relaxations. After treatment with DETCA, duroquinone produced greater reductions of relaxant responses to NO and to nitrergic stimulation, the IC50 values being 8.5 microM for NO and 40 microM for nitrergic nerve stimulation: these reductions were reversed by SOD. 6. The findings do not support the hypothesis that the presence of Cu/Zn SOD explains the greater susceptibility of NO than the nitrergic transmitter to the superoxide generator pyrogallol, but suggest that it may play a role in the effects of duroquinone. | Results: The ketamine-induced inhibition of the NANC relaxation was partly reversed by superoxide dismutase (200, 400 U/ml) but not by catalase (100 U/ml). Ketamine concentration-dependently inhibited the relaxation induced by N-ethylethanamine:1,1-diethyl-2-hydroxy-2-nitrosohydrazine (diethylamine NONOate) and S-nitrosoglutathione. The NANC relaxation itself was not affected by superoxide dismutase. The midazolam-induced inhibition of the NANC relaxation was reversed neither by superoxide dismutase nor by catalase, and midazolam did not affect the relaxations induced by nitric oxide donors. The nitric oxide synthase activity was concentration-dependently suppressed by midazolam, but there was no marked effect of ketamine. Pyrogallol, a superoxide generator, inhibited the NANC and the diethylamine NONOate-induced relaxations. The pyrogallol-induced inhibition of the NANC relaxation was reversed by superoxide dismutase. Conclusion: These findings suggest that ketamine inhibits NANC LES relaxation by the extracellular production of superoxide anion, and that midazolam inhibits it by the inhibition of | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,719 |
We have developed a rapidly acquired T1-weighted spin-echo pulse sequence that uses gradient echo-like parameters of TR 70 ms, TE 10 ms, NEX-1 (SE 70/10/1) with large pulse angles, and presaturation. This sequence yields two images of the abdomen during a comfortable breath-hold of 9 s. Preliminary phantom studies with this sequence demonstrated that peak signal-to-noise ratios occurred at pulse angles of 120° and 135°. Compared to this rapidly acquired sequence, a conventional T1-weighted spin-echo sequence of TR 140 ms, TE 10 ms, NEX-4 demonstrated 2.8 times the signal-to-noise ratio, 2.6 times the liver-spleen contrast-to-noise ratio but only 1.6 times the contrast-to-artifact ratio. When normalized for the imaging time, however, there was little difference in the signal-to-noise and contrast-to-noise ratios, although the SE 70/10/ 1 demonstrated 2.0 times the contrast-to-artifact ratio. We conclude that for abdominal imaging the SE 70/10/1 is an excellent alternative to RASE and other fast imaging techniques, and, although there are inherently low signal-to-noise ratios, it may be particularly useful when coupled with a paramagnetic contrast agent. | Twenty-nine patients with hepatic hemangiomas (n = 14) and hepatic metastases (n = 15) underwent magnetic resonance (MR) imaging prior to and after an intravenous bolus injection of Gd-diethylenetriamine pentaacetic acid (0.2 mmol/kg). Before contrast application, a T2-weighted spin echo sequence (SE 1,600/105) and a T1-weighted gradient echo sequence (GE 315/14/90 degrees pulse angle) were performed. Beginning with injection of the contrast agent, a dynamic study was conducted for 10 min using a moderately T1-weighted gradient echo sequence (GE 40/14/40 degrees) with an acquisition time of 10.2 s per image. Delayed (11 min) and late (60 min) postcontrast images were obtained using a T1-weighted sequence (GE 315/14/90 degrees). In the dynamic study (0-10 min) the hemangiomas were characterized by peripheral contrast enhancement and a subsequent hyperintense fill-in. The metastases showed very mixed patterns of enhancement after contrast administration, and their signal intensity remained low compared with that of the hepatic tissue. In the delayed postcontrast examination (11 min) the hemangiomas had a very high and homogeneous signal intensity and the metastases were characterized by an inhomogeneous, hypointense to isointense signal. The contrast between tumor and liver [signal-difference-to-noise ratio (SD/N)] was higher for all hemangiomas than it was for the metastases. In the T2-weighted precontrast examination, on the other hand, five hemangiomas and seven metastases showed an overlap in the SD/N. The late postcontrast images (60 min) did not yield any further diagnostic information. We conclude that the combination of a dynamic MR study with delayed postcontrast T1-weighted imaging is a useful method of diagnosing hepatic hemangiomas. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,720 |
Previous investigations have shown that the signal transducers and activators of transcription (STATs) signaling pathway play an important role in the modulation of apoptosis after ischemia and reperfusion. The mecha- nism for this enhanced cardioprotection is unknown, but we believe that alterations STATs may play a role.To inves- tigate this hypothesis, we examined the effects of angioten- sion II type 1 (AT1) and angiotension II type 2 (AT2) receptor antagonist added to cardioplegia on the down- stream response of different STATs, connected with proinflammatory pathways (STAT2, STAT5) and prohy- pertrophic and antiapoptotic pathways (STAT3). Isolated, nonworking hearts (n = 3 per group) from neonatal rats were perfused aerobically (4°C) for 20 min in the Langen- dorff mode with the modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 1), the MSTH2 car- dioplegic solution + AT1 receptor antagonist (Group 2), and MSTH2 cardioplegic solution + AT2 receptor antago- nist (Group 3). Thus, myocytes were isolated by enzymatic digestion, and STAT2, STAT3, and STAT5 were investi- gated in Western blot studies. Times to arrest after car- dioplegia were 8-12 s for all groups. Total cardioplegia delivery volume was about 300 mL for the 20 min. Perfu- sion with the MSTH2 cardioplegic solution supplemented with AT1 receptor antagonist (Group 2) induced a signifi- cant reduction in STAT2 and STAT5 tyrosine phosphory- lation (-58 and -63%, respectively, vs. Group 1, P < 0.05). Conversely, STAT2 and STAT5 activation were unaffected by perfusion with the MSTH2 cardioplegic solution supple- mented with AT2 receptor antagonist (Group 3). The decreased activation of STAT2 and STAT5 observed in Group 2 was accompanied by reduction of interleukin-1b (-57% in Group 2 vs. Group 1, P < 0.05). There were no significant differences in STAT3 phosphorylation among all groups. Only the addition of AT1 receptor antagonist to MSTH2 cardioplegia significantly decreases the inflamma- tory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by tyrosine phosphorylation of STAT3. AT1 receptor antagonist added to cardioplegia represents an additional modality for enhancing myocardial protection during cardiac surgery and could contribute to optimize the ischemia tolerance of the pediatric heart. Key Words: Rat myocardium— Cardioplegia—Angiotensin II antagonist—Valsartan— Signal transducers and activators of transcription. | Hypoxia/ischemia (HI) is a prevalent reason for neonatal brain injury with inflammation being an inevitable phenomenon following such injury; but there is a scarcity of data regarding the signaling pathway involved and the effector molecules. The signal transducer and activator of transcription factor 3 (STAT3) is known to modulate injury following imbalance between pro- and anti-inflammatory cytokines in peripheral and central nervous system injury making it a potential molecule for study. The current study investigates the temporal expression of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, IL-1ra, IL-4, IL-10, IL-13 and phosphorylated STAT3 (pSTAT3) after carotid occlusion and hypoxia (8% O2, 55 min) in postnatal day 7 C57BL/6 mice from 3 h to 21 days after hypoxia. Protein array illustrated notable changes in cytokines expressed in both hemispheres in a time-dependent manner. The major pro-inflammatory cytokines showing immediate changes between ipsi- and contralateral hemispheres were IL-6 and IL-1β. The anti-inflammatory cytokines IL-4 and IL-13 demonstrated a delayed augmentation with no prominent differences between hemispheres, while IL-1ra showed two distinct peaks of expression spread over time. We also illustrate for the first time the spatiotemporal activation of pSTAT3 (Y705 phosphorylation) after a neonatal HI in mice brain. The main regions expressing pSTAT3 were the hippocampus and the corpus callosum. pSTAT3+ cells were mostly a subpopulation of activated astrocytes (GFAP+) and microglia/macrophages (F4/80+) seen only in the ipsilateral hemisphere at most time points studied (till 7 days after hypoxia). The highest expression of pSTAT3+ cells was observed to be around 24-48 h, where the presence of pSTAT3+ astrocytes and pSTAT3+ microglia/macrophages was seen by confocal micrographs. In conclusion, our study highlights a synchronized expression of some pro- and anti-inflammatory cytokines, especially in the long term not previously defined. It also points towards a significant role of STAT3 signaling following micro- and astrogliosis in the pathophysiology of neonatal HI-related brain injury. In the study, a shift from pro-inflammatory to anti-inflammatory cytokine profile was also noted as the injury progressed. We suggest that while designing efficient neuroprotective therapies using inflammatory molecules, the time of intervention and balance between the pro- and anti-inflammatory cytokines must be considered. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,721 |
Background ::: Oxidative stress and smoking contribute to endothelial dysfunction. Iron might also play a role in oxidative stress generation and endothelial dysfunction. However, the involvement of iron in smoking-induced endothelial dysfunction in healthy smokers remains unclear. Therefore, we examined here whether (1) intravenous iron infusion impaired endothelial function evaluated by flow-mediated vasodilatation (FMD) in non-smokers, and (2) deferoxamine, a potent iron chelator, ameliorated endothelial dysfunction in healthy smokers. ::: Methods ::: Eight healthy young male non-smokers (23±4 years old) received intravenous injection of saccharated ferric oxide (0.7 mg/kg body weight), while 10 age-matched healthy male smokers received deferoxamine mesylate (8.3 mg/kg body weight). At baseline, 5 and 20 minutes after treatment with iron or deferoxamine, biochemical variables were measured, including serum iron and marondialdehyde (MDA), a marker of lipid oxidation, and endothelial function was simultaneously evaluated by FMD. ::: Results ::: Compared with non-smokers, FMD was significantly lower in smokers. Iron and MDA levels were significantly increased, whereas FMD was impaired by iron infusion in non-smokers. Conversely, deferoxamine treatment significantly decreased iron and MDA levels and restored the decreased FMD in smokers. Baseline serum iron and MDA levels in all 18 subjects (non-smokers and smokers) were correlated with each other. There was a significant inverse correlation between the changes in MDA values and FMD from baseline in 18 men. Endothelium-independent vasodilation by glyceryl trinitrate was unaltered by either treatment. ::: Conclusions ::: Our present study suggests that iron-evoked oxidative stress might play a role in endothelial dysfunction in healthy smokers. | This paper is an overview on iron metabolism, iron toxicity and therapeutics against this toxicity. The attention has been focused on: i) the solubilization of iron by living organisms; ii) the iron metabolism in human; iii) the toxicity of iron (Fe-catalyzed reduction of oxygen, Fenton reaction, decomposition of lipid peroxides); iv) the natural protective mechanisms; v) the relations between iron, free radicals and human diseases; and vi) the iron overload and its treatment. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,722 |
Objective:To investigate the effect of panax notoginseng saponins(PNS) on cerebral ischemia reperfusion injury in rats.Method:SD rats were divided into sham operation group,model group,PNS group.Model group and PNS group were established ischemia-reperfusion injury by using ligation of middle cerebral artery.PNS was given 15 min before ischemia and 6 h after ischemia,respectively,ip PNS 100 mg·kg-1 for rats in PNS group.Rats in model group and sham group were given at the same time ip with normal saline.The neurologic deficit score,brain infarction size and the levels of interleukin-1β(IL-1β),tumor meerosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-8(IL-8) and content of Evans blue in brain tissue were examined.Result:PNS could reduce infarct volume of cerebral ischemia-reperfusion injury in rats,reduce the extent of the damage in blood-brain barrier significantly.The levels of cytokines and content of Evans blue in PNS group were successively decreased as compared with those in model group(P0.05).Conclusion:PNS has a significant brain protection on ischemia-reperfusion injury.PNS has significant effect of reducing the levels of cytokines,PNS can also reduce the permeability of blood-brain barrier. | The present study monitored the effect of 2, 10, and 50 mg/L of Panax notoginseng saponin exposure following hypoxia-reoxygenation injury in fetal rat cortical neurons. Results showed that varying doses of Panax notoginseng saponin significantly enhanced the cell viability of neurons, reduced malondialdehyde content, increased superoxide dismutase activity, inhibited mRNA and protein expression of inducible and neuronal nitric oxide synthase, and decreased the release of nitric oxide in hypoxia/reoxygenation injured cells. In particular, 50 mg/L of Panax notoginseng saponin was the most effective dose. These findings suggest that Panax notoginseng saponin can attenuate neuronal oxidative stress injury caused by hypoxia/reoxygenation in a dose-dependent manner. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,723 |
Therapeutic antitumor immunity depends on a highly migratory CTL population capable of activation and trafficking between lymphoid and tumor-bearing microanatomic sites. We recently adapted positron-emission tomography gene expression imaging for noninvasive, longitudinal localization and quantitation of antitumor T lymphocyte migration in vivo. In this study, we apply this system to enumerate the temporal accumulation of naive vs memory T cells. Naive or memory OT-1 CD8(+) T cells, retrovirally marked with the sr39TK gene, were adoptively transferred into RAG1(-/-) animals bearing EL-4 or EG.7 (an OVA-expressing subline), and repetitively imaged by microPET over several weeks. Memory cells demonstrated early accumulation and apparent proliferation, with large T cell numbers at the Ag-positive tumor as early as day 1 after T cell transfer. Naive T cells did not accumulate in the E.G7 tumor until day 8, and reached only 25% of the peak levels achieved by memory T cells. Both naive and memory cells eradicated the Ag-expressing tumor at a comparable density of intratumoral T cells (2-4 x 10(6)/g). However, due to the slower rate of T cell expansion and continued tumor growth, naive cells required approximately 10-fold higher Ag-specific precursor frequency to reach a tumoricidal cell density. As recently reported, memory but not naive T cells accumulated in local lymph nodes and lungs, where they persisted as a resident population after tumor eradication. Positron-emission tomography-based immunologic imaging is a noninvasive modality providing unique and meaningful information on the dynamics of the antitumor CTL response. | Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8+ cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instantaneous velocities. The CTLs arrest in close contact to tumor cells expressing their cognate antigen. In regions where most tumor cells are dead, CTLs resume migration, sometimes following collagen fibers or blood vessels. CTLs migrating along blood vessels preferentially adopt an elongated morphology. CTLs also infiltrate tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the cognate antigen, CTL infiltration is restricted to peripheral regions, and lymphocytes neither stop moving nor kill tumor cells. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and profound tumor infiltration. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,724 |
The old concept that the lacrimal gland is only a serous gland has been superseded by the finding that lacrimal acinar cells are able to produce mucins— high‐molecular‐weight proteins—the major mass being carbohydrates with the common feature of tandem repeats of amino acids rich in serine, threonine, and proline in the central domain of the mucin core peptide. At the ocular surface, maintenance of the tear film, lubrication, and provision of a pathogen barrier on the epithelia, conjunctiva, and cornea have been shown to be facilitated by mucins that are present in membrane‐anchored (lining epithelial cells) or secreted (goblet cells) form. Also in the lacrimal gland, both membrane‐anchored (MUCs 1, 4, and 16) and secreted (MUCs 5B and 7) mucins have been identified. The lacrimal gland is the main contributor to the aqueous portion of the tear film. It is part of the lacrimal apparatus that comprises, together with the lacrimal gland, the paired lacrimal canaliculi, the lacrimal sac, and the nasolacrimal duct, which collects the tear fluid and conveys it into the nasal cavity. In this review, the latest information regarding mucin function in the human lacrimal gland and the human efferent tear ducts is summarized with regard to mucous epithelia integrity, rheological and antimicrobial properties of the tear film and tear outflow, age‐related changes, and certain disease states such as the pathogenesis of dry eye, dacryostenosis, and dacryolith formation. | Hairdressers are frequently exposed to bleaching powder containing persulfates, a group of compounds that may induce hypersensitivity in the airways. The mechanism causing this reaction is not clear. The aim of this study was to identify changes in the nasal lavage fluid proteome after challenge with potassium persulfate in hairdressers with bleaching powder-associated rhinitis. Furthermore, we aimed to compare their response to that of hairdressers without nasal symptoms, and atopic subjects with pollen-associated nasal symptoms. To study the pathogenesis of persulfate-associated rhinitis, the response in protein expression from the upper airway was assessed by time-dependent proteomic expression analysis of nasal lavage fluids. Samples were prepared by pooling nasal lavage fluids from the groups at different time points after challenge. Samples were depleted of high-abundant proteins, labeled with iTRAQ and analyzed by online 2D-nanoLC-MS/MS. Differences in the protein pattern between the three groups were observed. Most proteins with differentially expressed levels were involved in pathways of lipid transportation and antimicrobial activities. The major finding was increased abundance of apolipoprotein A-1, 20 min postchallenge, detected solely in the group of symptomatic hairdressers. Our results suggest there may be differences between the mechanisms responsible for the rhinitis in the symptomatic and atopic group. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,725 |
Introduction: Although disseminated intravascular coagulation (DIC) is an “intermediary mechanism of disease”1 that has been intensively studied during the last three decades,2-4 several aspects relating to the clinical problem of DIC are still under debate. For example, a standardized definition of disseminated intravascular coagulation has not yet been agreed upon. A diagnosis can be accurately made using the facilities of a specialized laboratory, but time constraints make the diagnosis of DIC by the general laboratory difficult. Since DIC can be prevented if the right therapy is initiated early, the ability to quickly and accurately diagnose DIC and to monitor the involved dynamic processes are essential prerequisites for the effective management patients with DIC. Due to the problems associated with defining DIC, making an early diagnosis, and effectively treating the condition following diagnosis, the clinical management of DIC can be difficult. The transition from an activated hemostatic system to a well-defined state of DIC is indistinct, and the borderlines cannot easily be distinguished. In addition, different underlying diseases mediating DIC induce different clinical symptoms associated with DIC and demand different therapeutic approaches. | Plasma levels of granulocyte-derived elastase (GE-XDP), D-dimer, and soluble fibrin (SF) were examined in 177 patients with disseminated intravascular coagulation (DIC) of various etiologies. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with sepsis and solid cancer. The ratio of GE-XDP/D-dimer was significantly high in patients with trauma, burn, and sepsis, suggesting that fibrinolysis due to GE-XDP may be dominant in DIC. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with overt DIC and correlated with DIC score. Plasma levels of GE-XDP, but not SF, correlated significantly with D-dimer. Plasma levels of D-dimer, but not SF, correlated significantly with plasmin plasmin inhibitor complex (PPIC). Plasma levels of GEXDP and D-dimer, but not SF, were significantly high in nonsurvivors. Plasma levels of GE-XDP, but not SF, correlated significantly with sepsis-related organ failure assessment (SOFA) score. These results suggest tha... | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,726 |
The release of inflammatory cytokines has been implicated in the toxicity of conventional radiotherapy (CRT). Transforming growth factor β (TGF-β) has been suggested to be a risk marker for pulmonary toxicity following radiotherapy. Pulsed low-dose rate radiotherapy (PLDR) is a technique that involves spreading out a conventional radiotherapy dose into short pulses of dose with breaks in between to reduce toxicities. We hypothesized that the more tolerable toxicity profile of PLDR compared with CRT may be related to differential expression of inflammatory cytokines such as TGF-β in normal tissues. To address this, we analyzed tissues from mice that had been subjected to lethal doses of CRT and PLDR by histology and immunohistochemistry (IHC). Equivalent physical doses of CRT triggered more cellular atrophy in the bone marrow, intestine, and pancreas when compared with PLDR as indicated by hematoxylin and eosin staining. IHC data indicates that TGF-β expression is increased in the bone marrow, intestine, and lungs of mice subjected to CRT as compared with tissues from mice subjected to PLDR. Our in vivo data suggest that differential expression of inflammatory cytokines such as TGF-β may play a role in the more favorable normal tissue late response following treatment with PLDR. | This work aimed to evaluate the in vivo capacity of a vegetable oil blend formulation (VOB) developed to accelerate cutaneous wound closure. Total thickness wounds were punctured on the skin on the back side of each animal and topically treated with the VOB formulation, Dersani® ointment or the vehicle control. After 2, 7, 14, 21 days post-wounding, five animals from each group were euthanized, and the rates of wound closure and re-epithelialization were evaluated. The wounds were harvested for histological and biochemical analysis. VOB resulted in faster and greater re-epithelialization in the in vivo excisional wounds, exhibiting significant wound area reduction of 8.9, 8.0, 35.1, 45.2 and 47.0% after 2, 5, 10, 14 and 21 days post-wounding, respectively, when compared with the vehicle control. Histological and biochemical analyses showed that the VOB-treated wounds exhibited a significant increase of granular tissue and controlled inflammatory response by modulation of the release of pro-inflammatory cytokines TNF-α, IL-6 and IL-1. Moreover, VOB-treated wounds showed a significant and concrete increase in the deposition and organisation of collagen fibres in the wound site and improved the quality of the scar tissue. Altogether, these data revealed that VOB accelerates wound healing processes and might be beneficial for treating wound disorders. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,727 |
ETHNOPHARMACOLOGICAL RELEVANCE ::: Schisandra chinensis fruit is widely used in Chinese medicine for the treatment of hepatic, renal, heart, cerebrovascular and infectious diseases. ::: ::: ::: AIM OF THE STUDY ::: To investigate the effects of Schisandra chinensis fruit extract (SE) on albuminuria and podocyte injury as well as the underlying mechanism in the mouse model of streptozotocin (STZ)-induced diabetic nephropathy and in cultured mouse podocyte cells. ::: ::: ::: MATERIALS AND METHODS ::: SE was orally administrated in STZ-induced diabetic nephropathy mice for 7 weeks, at a daily dose of 5g/kg body weight. The urinary albumin/creatinine ratio and urine albumin excretion rate were measured at the 6th and 9th week of the experiment. The extent of glomerulosclerosis and extracellular matrix deposition were determined by periodic acid-silver methenamine and Masson's trichrome staining. The amount of podocytes and the integrity of the slit diaphragm were detected by immunohistological staining of podocyte markers, Wilms' tumor 1 and nephrin. Alpha-smooth muscle actin, E-cadherin and plasminogen activator inhibitor-1 were measured by western blot and immunohistological staining to evaluate the level of epithelial-to-mesenchymal transition (EMT). Real-time reverse transcription PCR was used to detect the mRNA level of E-cadherin, alpha-SMA and snail in cultured podocyte cells. ::: ::: ::: RESULTS ::: Treatment with SE significantly decreased the urine albumin excretion rate and urinary albumin/creatinine ratio. In addition, SE attenuated glomerulosclerosis and protected against podocyte loss and integrity of the slit diaphragm. Furthermore, SE effectively prevented the EMT of podocytes caused by diabetic nephropathy. ::: ::: ::: CONCLUSIONS ::: Our studies suggest that SE might be beneficial for diabetic nephropathy. The effects of SE on attenuating albuminuria and glomerulosclerosis are possibly mediated by preserving podocyte integrity through suppressing EMT. | The aims of this study were to explore the effects of Astragaloside IV on diabetic nephropathy (DN) rats. A total of 38 male Sprague-Dawley (SD) rats were divided into three groups: 10 in the normal (control) group, 14 in the DN model group, and 14 in the AS-IV group. Treatment began one week after the streptozotocin DN model was successfully established. Blood glucose and urine micro-albumin levels were measured every four weeks. After being treated for 12 weeks, all SD rats were sacrificed for blood and renal specimen collec-tion. Renal cortex specimens were observed after hematoxylin and eo-sin and Masson staining. Expression levels of protein β1, β1-integrin-linked protein kinase (ILK) and α-actinin-4 were also measured. After eight weeks of intervention, blood glucose levels in the AS-IV group decreased significantly when compared with those of the model group (P < 0.01). By the end of the twelfth week, the urine micro-albumin levels showed significant differences (P < 0.01) between the AS-IV and model groups, and the expression levels of integrin β1, ILK, and α-actinin-4 also showed significant differences (P < 0.05, respectively). Concomitantly, expression levels of integrin β1, ILK, and α-actinin-4 in the model group were significantly different from those of normal group (P < 0.05). These results suggest that AS-IV can be quite effective in decreasing blood glucose levels, reducing urine albumin excretion, and improving the adhesion function of potocytes, and can thus delay the development of DN. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,728 |
BACKGROUND ::: Allergic sensitisation increases the risk for asthma development. In this prospective birth cohort (Environment and Childhood Asthma) study, we hypothesized that combining quantitative measures of IgE antibodies (Sigma-IgE) and Severity score of obstructive airways disease (OAD) at 2 years of age (Severity score) is superior to predict current asthma (CA) at 10 years than either measure alone. Secondarily, we assessed if gender modified the prediction of CA. ::: ::: ::: METHODS ::: A follow-up study at 10 years of age was performed in 371 2-year-old children with recurrent (n = 219) or no (n = 152) bronchial obstruction with available serum analysed for Sigma-IgE to common food and inhalant allergens through a panel test, Phadiatop Infant) (Phadia, Uppsala, Sweden). Clinical variables included allergic sensitisation and exercise testing to characterise children with CA vs not CA at 10 years and the Severity score (0-12, 0 indicating no OAD) was used to assess risk modification. ::: ::: ::: RESULTS ::: Severity score alone explained 24% (Nagelkerke R(2) = 0.24) of the variation in CA, whereas Sigma-IgE explained only 6% (R(2) = 0.06). Combining the two increased the explanatory capacity to R(2) = 0.30. Gender interacted significantly with Sigma-IgE; whereas Severity score predicted CA in both genders, the predictive capacity of Sigma-IgE for CA at 10 years was significant in boys only. ::: ::: ::: CONCLUSION ::: Combining Sigma-IgE to inhalant allergens and Severity score at 2 years was superior to predict asthma at 10 years than either alone. Severity score predicted CA in both genders, whereas Sigma-IgE significantly predicted CA in boys only. | Many children suffer from recurrent coughing, wheezing and chest tightness. In preschool children one third of all children have these symptoms before the age of six, but only 40% of these wheezing preschoolers will continue to have asthma. In older school-aged children the majority of the children have asthma. Quality of life is affected by asthma control. Sleep disruption and exercised induced airflow limitation have a negative impact on participation in sports and social activities, and may influence family life. The goal of asthma therapy is to achieve asthma control, but only a limited number of patients are able to reach total control. This may be due to an incorrect diagnosis, co-morbidities or poor inhalation technique, but in the majority of cases non-adherence is the main reason for therapy failures. However, partnership with the parents and the child is important in order to set individually chosen goals of therapy and may be of help to improve control. Non-pharmacological measures aim at avoiding tobacco smoke, and when a child is sensitised, to avoid allergens. In pharmacological management international guidelines such as the GINA guideline and the British Guideline on the Management of Asthma are leading. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,729 |
Homocystinuria was diagnosed in 12 patients, aged 3-12 years. Myopia, ranged from -5.0 D to -20.0 D, and bilateral subluxation of lens were found in all children. In 8 eyes during follow-up luxation of lens was observed in 8 eyes, in 5 complicated by acute glaucoma. Surgical treatment, mostly pars plana lensectomia, was applied in 20 eyes. Normalisation of the intraocular pressure was achieved after surgery in 4 cases and improvement of visual acuity in 16 eyes. In 1 case of a boy after cerebral vessels infarct the intraocular pressure remained elevated and optic nerve atrophy developed. In 3 cases anterior scleral staphyloma was found. | The authors review ten essential amino acids with regard to their metabolic, physiologic and therapeutic effects throughout the human body. Physical properties of these biologically active compounds are discussed as a foundation for their diverse roles in special nitrogen containing products, neurotransmitters, and as alternative energy sources. Both normal and abnormal amino acid metabolism are considered in the areas of digestion, elimination of metabolic products, metabolic intermediates, and defects in these systems. Recent developments in therapeutic applications are further examined for clinical utility and as an economical alternative to traditional clinical treatment modalities. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,730 |
A single injection of angiotensin (0.5 µg) into the lateral ventricle of unanesthetized adult rats elevates mean blood pressure approximately 33 mm Hg. This effect, enhanced by hexamethonium administered peripherally, is inhibited by hexamethonium administered centrally. Phenoxybenzamine pretreatment is also inhibitory. Hypophysectomy reduces central pressor activity approximately 50% and ganglionic blockade abolishes the remaining activity. Lesions in the supraoptic nuclei decrease central pressor activity to the values obtained in hypophysectomized animals. Concomitant with its central pressor effect, angiotensin produces neurogenic thirst which can be markedly inhibited by anticholinergic drugs. These data suggest that angiotensin interacts with central neurons to cause release of antidiuretic hormone and polydipsia which, in the absence of compensatory mechanisms, might produce positive water balance. | It has become increasingly evident that blood-borne angiotensin II has major effects upon brain cardiovascular centers. With the discovery of an angiotensin I-forming enzyme or isoenzymes in the central nervous system of mammals, alternative concepts have emerged regarding the role of this peptide in the regulation of central adrenoreceptor activity, pituitary function, and hydromineral metabolism. These concepts are reviewed, and a framework for future research is suggested by the author. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,731 |
INTRODUCTION ::: Beta 2 microglobulin (beta2M) is filtered by the glomeruli and reabsorbed by the proximal tubular cells where it is metabolized. Its plasma concentration increases with decreasing renal function. ::: ::: ::: AIM ::: To compare serum creatinine (Cr) and serum beta2M as markers of GFR. ::: ::: ::: PATIENTS AND METHODS ::: In 160 adult patients, with various kidney diseases and different GFR, serum Cr (autoanalyzer), serum beta2M (RIA) and GFR (bladder cumulative method using 99mTc-DTPA as glomerular tracer) were measured in the same day. ::: ::: ::: RESULTS ::: A linear relationship was observed between In GFR and both In serum Cr (lnCr=3.112-0.716 lnGFR; r=0.92) and ln serum beta2M (lnbeta2M= 4.274-0.814 lnGFR; r = 0.90). With decreasing GFR the increase in serum beta2M was higher than that of serum Cr (see regression coefficients that are significantly different). The normal upper limit of serum Cr corresponds to a GFR 48.1 mL/min while that of serum beta2M to a GFR 65.0. With decreasing GFR the increase of serum beta2M occurs before than that of serum Cr. ::: ::: ::: CONCLUSIONS ::: With declining renal function, serum beta2M increases more and before than serum Cr. Serum beta2M is a good endogenous marker of GFR, better than serum Cr. | Background ::: Beta-2 Microglobulin (β2M) is a prototypical “middle molecule” uremic toxin that has been associated with a higher risk of death in hemodialysis patients. A quantitative description of the relative importance of factors determining β2M concentrations among patients with impaired kidney function is currently lacking. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,732 |
Although a wealth of evidence has suggested that cell-mediated immunity is suppressed after simple surgical trauma, there have been contradictory results using stimulation assays of lymphocyte function. We quantitated T-lymphocyte subsets in 11 patients undergoing routine cholecystectomy by immunofluorescence microscopy using specific monoclonal antibodies. T-helper to T-suppressor cell ratios were calculated on the preoperative day and the first postoperative day in all patients, and on the third or fourth postoperative day in five patients. Helper to suppressor ratios decreased in all patients on the first postoperative day (p greater than 0.01), but returned to within normal limits on subsequent days. Changes were due more to decreases in helper cells than to increases in suppressor cells, although changes in both populations were statistically significant. The measurement of T-cell subsets by antibody-specific labeling and immunofluorescence microscopy may prove to be a more sensitive, quantifiable, and reproducible assay of immune function in surgical or traumatized patients than use of stimulation assays. Measurements of specific helper and suppressor lymphocyte populations may prove useful in predicting morbidity and mortality, and may also help in studying the effect of immunomodulating agents on the immune response. | The aim of this study was to ascertain postoperative changes in immunoglobulin E (IgE) in patients undergoing different types of surgery and the possible correlation with the duration and type of surgery. Evidence suggests that surgery induces a predominant activation pattern through the T-helper-2 (Th2) cell pathway, increasing interleukins (IL-4, IL-5, IL-10, IL-13), inhibiting Th1 cell activation, and promoting B and Th2 cell activation. IgE production may indicate predominant Th2 pathway activation and may be a more persistent and easily measurable postoperative marker than IL-6 for measuring surgical trauma. Altogether, 180 patients undergoing different types of surgery for nonneoplastic and nonparasitic diseases were studied. All patients received the same type of anesthesia. Before surgery and on the first (1PO) and 7th (7PO) postoperative days we determined in peripheral blood the CD3, CD4, CD8, CD16, and CD19 cell percentages; IL-1, IL-2, IL-4, IL-6, and tumor necrosis factor (TNF) levels; and the IgA, IgG, IgM, total IgE, C3, C4, and CIC levels. On 1PO, all variables decreased except IgE, IL-1, IL-2, IL-4, IL-6, CIC, and CD19. Only IgE, IL-6, and CD19 increases showed a significantly statistical (ss) difference regarding preoperative values (0.01, 0.05, 0.001, respectively). Relations between the IL-4 and IgE increases (p < 0.01) and between the IgG decrease and IgE increase (p < 0.001) were found. On 7PO, only IgE was increased (p < 0.001). The IgE increase correlated with surgical trauma intensity (p < 0.05). We concluded that IgE increases during the early postoperative period, correlating with surgical injury intensity. The increase in the IgE level may be detected 24 hours after surgery and during the first 7 postoperative days depending on the type of surgery. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,733 |
Nowadays non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver pathology both in adults and children. NAFLD manifestation ranges from a simple liver steatosis to steatohepatitis (nonalcoholic steatohepatitis - NASH), which may progress to advanced fibrosis, cirrhosis and end-stage liver disease. Due to the coexistence of visceral obesity, insulin resistance and dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome. In recent years, in the pathogenesis of metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease and also NAFLD, more and more attention has been paid to the so-called organokines, proteins with both paracrine or/and endocrine activities. These include most known adipokines (mainly produced by adipose tissue), myokines (mainly produced by skeletal muscles) and hepatokines exclusively or predominantly produced by the liver. It was shown that the liver may affect the lipids and glucose metabolism by hepatokines released into the blood and NAFLD seems to be associated with altered hepatokines production. Fetuin-A, fibroblast growth factor-21 (FGF-21), selenoprotein P, sex hormone-binding globulin (SHBG), angiopoietin-related growth factor (also known as angiopoietin-related protein 6) and leukocyte derived chemotaxin 2 (LECT2) are considered as the most important hepatokines. In this review, we provide an overview of the main hepatokines and we summarize the association of liver-derived proteins with the development and progression of NAFLD. | Objective ::: To investigate the association between serum fetuin A concentration and non-alcoholic fatty liver disease (NAFLD) in Chinese population. ::: ::: ::: Methods ::: This case-control study enrolled 79 NAFLD cases and 79 non-NAFLD controls. All subjects were selected from Chinese population who received annual health examination in the First Affiliated Hospital of Zhejiang University in 2016. NAFLD was diagnosed mainly based on abdominal ultrasonography. The severity of NAFLD was categorized by serum level of alanine aminotransferase. Serum fetuin A was measured by ELISA. ::: ::: ::: Results ::: Serum fetuin A level in NAFLD patients was significantly lower than that in controls (0.27±0.17 vs. 0.32±0.12g/L, P < 0.05). Compared with controls, mild NAFLD (0.24±0.16 g/L, P < 0.05) and moderate NAFLD (0.25±0.17 g/L, P < 0.05) had significantly lower concentration of Fetuin A, while Fetuin A level tended to slightly increase with the severity of NAFLD. The prevalence rate of NAFLD decreased (75 %, 40 %, and 36 %), as Fetuin A level elevated. ROC curve of Fetuin A was developed to predict the presence of NAFLD. Area under ROC was 0.656. ::: ::: ::: Conclusion ::: Serum level of Fetuin A was lower in NAFLD patients than controls, while Fetuin A level increased with the severity of NAFLD, indicating a potential predicting role of Fetuin A in the development of NAFLD. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,734 |
AIMS ::: To inform patients and their carers about both the probability of reducing glycated haemoglobin (HbA1c) to clinically desirable levels and the sustainability of such control over 2 years with major second-line antidiabetic therapies, in individual risk scenarios, with and without third-line intensification. ::: ::: ::: MATERIALS AND METHODS ::: From US Centricity Electronic Medical Records, 163 081 patients with type 2 diabetes aged 18 to 80 years, who had initiated metformin, intensified their treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), sulphonylureas (SUs), insulin or thiazolidinediones (TZDs), and continued second-line treatment for ≥6 months, were selected. Treatment groups were balanced with regard to baseline characteristics, and glycaemic achievements were estimated using logistic regression analysis. ::: ::: ::: RESULTS ::: With HbA1c concentrations of 58-63.9 mmol/mol (7.5-7.9%) at second-line treatment initiation, the adjusted probabilities of achieving HbA1c <53 mmol/mol (<7%) at 6 months were 32%, 38%, 39%, 26% and 38% in the SU, DPP-4 inhibitor, GLP-1RA, insulin and TZD groups, respectively, while with baseline HbA1c concentrations of 64-75 mmol/mol (8-9%), the corresponding probabilities of reducing HbA1c to <58 mmol/mol (<7.5%) were 38%, 44%, 40%, 34% and 42%, respectively. In these baseline HbA1c categories, the adjusted probabilities of sustaining HbA1c achievements over 2 years were higher in the GLP-1RA and TZD groups, compared with the SU and insulin groups (P < .01). With baseline HbA1c concentrations of 75.1-108 mmol/mol (9.1-12%) 38% of patients achieved an HbA1c concentration <58 mmol/mol (<7.5%) at 6 months. The adjusted probability of sustaining this control over 2 years was higher in the incretin and TZD groups (range 62%-75%), while insulin and SUs offered lower chances of sustainable control (range 54%-56%). ::: ::: ::: CONCLUSIONS ::: Patients treated with second-line incretins and TZDs had a significantly higher probability of achieving and sustaining glycaemic control over 2 years without further intensification, compared with those treated with SUs or insulin. | Despite U.S. Food and Drug Administration (FDA) approval of over 40 new treatment options for type 2 diabetes since 2005, the latest data from the National Health and Nutrition Examination Survey show that the proportion of patients achieving glycated hemoglobin (HbA 1c ) 1c 1c reductions fell far short of those reported in randomized clinical trials (RCTs), with poor medication adherence emerging as the key driver behind the disconnect. In this Perspective, we examine the implications of these findings in conjunction with other data to highlight the discrepancy between RCT findings and the real world, all pointing toward the underrealized promise of FDA-approved therapies and the critical importance of medication adherence. While poor medication adherence is not a new issue, it has yet to be effectively addressed in clinical practice—often, we suspect, because it goes unrecognized. To support the busy health care professional, innovative approaches are sorely needed. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,735 |
BACKGROUND ::: Pustulosis palmaris et plantaris (PPP) is a chronic inflammatory disease consisting of polymorphonuclear leukocyte infiltration, and is often exacerbated by focal infections such as tonsillitis. In some cases, metal allergy has been reported. ::: ::: ::: OBJECTIVE ::: The purpose of this study was to evaluate (1) the significance of metal allergy in the formation of pustules, and (2) the participation of leukotriene (LT) B(4) in the formation of pustules of PPP. ::: ::: ::: METHODS ::: Patch tests with metals were performed on 7 patients with PPP, and both pustular and plasma levels of LTB(4) were measured in these 7 patients before and 48 hours after metal patch tests. ::: ::: ::: RESULTS ::: Palmoplantar pustules were exacerbated after the metal patch tests in all 7 patients. The mean levels of LTB(4) in plasma and pustules of the volar surface at 48 hours after the metal patch tests were significantly higher than those before the metal patch tests. ::: ::: ::: CONCLUSION ::: Metals can be important in the pathogenesis of PPP by contributing to the induction of high LTB(4) concentration in the pustules. | Palmoplantar pustulosis (PPP) is difficult to treat. There is little hard evidence for the efficacy of any treatment and no published guidelines for its management. A number of exacerbating factors are well documented and there is some evidence for the importance of others. Smoking is the most recognized environmental trigger and recent research has concentrated on the role of eccrine sweat glands in this regard. Other factors, including tonsillar streptococcal infection and gluten sensitivity, may be important in selected cases. The aim of this review is to challenge dermatologists to consider alternative management strategies for PPP and design clinical trials that will enable the development of useful therapeutic guidelines. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,736 |
Sickle cell disease (SCD) imparts an increased risk for obstructive sleep apnea (OSA) in childhood. Studies of pediatric SCD have identified an increased risk for pain and neurologic complications with comorbid OSA. We determined the rate of a broad range of SCD-related medical complications to better characterize the spectrum of SCD complications related to OSA. Retrospective chart review at a single hematology clinic identified 641 youth with SCD who received consistent screenings for OSA as part of routine hematological health maintenance visits over an 11-year period. Medical complication rates in the 136 children with OSA determined by polysomnography exams were compared to 136 matched controls at lower risk for OSA due to negative OSA screenings or exams. Children with SCD and OSA had higher overall rates of SCD complications than low OSA-risk controls; lung morbidity showed the largest effect size. Infection, cardiovascular, and neurologic complications occurred at higher rates in children with OSA. Children with comorbid OSA had higher rates of SCD complications both before and after OSA diagnosis. OSA in children with SCD is associated with higher rates of a broad range of SCD complications, including pneumonia and acute chest syndrome. Routine screenings, diagnosis, and increased therapeutic intervention for children with comorbid OSA could decrease SCD morbidity. | Hemolysis, long discounted as a critical measure of sickle cell disease severity when compared with sickle vaso-occlusion, may be the proximate cause of some disease complications. New mechanistic information about hemolysis and its effects on nitric oxide (NO) biology and further examination of the subphenotypes of disease requires a reappraisal and deconstruction of the clinical features of sickle cell disease. The biology underlying clinical phenotypes linked to hemolysis may increase our understanding of the pathogenesis of other chronic hemolytic diseases while providing new insights into treating sickle cell disease. The pathophysiological roles of dysregulated NO homeostasis and sickle reticulocyte adherence have linked hemolysis and hemolytic rate to sickle vasculopathy. Nitric oxide binds soluble guanylate cyclase which converts GTP to cGMP, relaxing vascular smooth muscle and causing vasodilatation. When plasma hemoglobin liberated from intravascularly hemolyzed sickle erythrocytes consumes NO, the normal balance of vasoconstriction:vasodilation is skewed toward vasoconstriction. Pulmonary hypertension, priapism, leg ulceration and stroke, all subphenotypes of sickle cell disease, can be linked to the intensity of hemolysis. Hemolysis plays less of a role in the vaso-occlusive-viscosity complications of disease like the acute painful episode, osteonecrosis of bone and the acute chest syndrome. Agents that decrease hemolysis or restore NO bioavailability or responsiveness may have potential to reduce the incidence and severity of the hemolytic subphenotypes of sickle cell disease. Some of these drugs are now being studied in clinical trials. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,737 |
The Role and Analysis of Benefit and Risk in the Development of New Drugs, C. Chuang-Stein Prediction of the Benefit/Risk Ratio from In Vitro Data, R. Shrivastava, C. Bonnabry, and G. John Evaluation of Therapeutic Benefits and Toxicological Risks Using Structure-Activity Relational Expert Systems, H.S. Rosenkranz, G. Klopman, and O.T. Macina Improving the Therapeutic Index Through Unusual Routes of Application: Intra-Arterial Treatment of Liver Metastases, D. Civalleri, G. Numico, F. DeCian, and M. Esposito Establishing the Benefit/Risk Ratio with Combination Drugs, A. Thurmann and J. Hasford Improving the Therapeutic Index of Antineoplastic Agents through Additional Drugs, G. Numico, D. Civalleri, and M. Esposito Antihypertensive Agents, B. Schwartzkopff and B.E. Strauer Diuretics, J. Zhi Anti-Diabetic Drugs, P. Compagnucci and F. Santeusanio Anticonvulsant Drugs and Drugs for Parkinson's Disease, M.J. Eadie Antihistamines and Antiserotonins, G. Passalcqua and G.W. Canonica Cytokines and Immunomodulators, D.J. Peace, W. Wong, and K.T. Ferrer Non-Opioid Analgesics and Anti-Inflammatory Agents, G. Traversa and N. Magrini Toxicity Profile of Liposomal Anthracyclines, A. A. Gabizon Antibacterial Agents, R. Garraffo Antiviral Agents, J.M. Kilby Antifungal Agents, A.K. Gupta, P. De Doneker, and M. Heenen Drugs Used in Reproductive Endocrinology, J.F. Mortola Nicotine Preparations in Smoking, N.L. Benowitz and J. Pinney Systemic Drugs for Skin Diseases, H. Bocquet, L. Le Cleach, and J.-C. Roujeau Topical Liposome Drugs, H.C. Korting Topical Glucocorticoids, M. Schafer-Korting and A. Gysler Index | Purpose: The present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (C trough) and microorganism-specific (AUC 24/MIC) targets over two weeks of teicoplanin administration according to several dose regimens for the treatment of Staphylococcus aureus in Korean patients with neutropenic fever. Materials and Methods: One thousand virtual concentrations were obtained for each dose using the population pharmacokinetic parameters of teicoplanin adopted from a published study. Simulation of 1,000 virtual MICs was performed using the MICs of 78 clinical isolates of S. aureus collected from a hospital in Korea. Thereafter, these simulated MICs were randomly allocated to 1,000 virtual patients in whom the TARs for AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L were determined. The relationship of the maintenance dose with the steady-state TAR was predicted with respect to the AUC24/MIC >125 [or 345] using logistic analysis. Results: The standard dose regimen of teicoplanin showed TARs of about 70% [or 33%] and 70% [or 20%] at steady-state in cases with AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L, respectively. Conclusion: The current standard dose regimen was predicted to be insufficient to adequately treat S. aureus in Korean patients with neutropenic fever. To assure at least an 80% TAR in this population, dose adjustment of teicoplanin should be considered. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,738 |
ABSTRACTIntroduction: Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune and systemic inflammatory diseases with both licensed and off-label indications. The mechanism of action is complex and not fully understood, involving the neutralization of pathological antibodies, Fc receptor blockade, complement inhibition, immunoregulation of dendritic cells, B cells and T cells and the modulation of apoptosis.Areas covered: First, this review describes the pharmacological properties of IVIg, including the composition, mechanism of action, and adverse events. The second part gives an overview of some of the immune-mediated polyneuropathies, with special focus on the pathomechanism and clinical trials assessing the efficacy of IVIg. A literature search on PubMed was performed using the terms IVIg, IVIg preparations, side effects, mechanism of action, clinical trials, GBS, CIDP.Expert opinion: Challenges associated with IVIg therapy and the treatment possibilities for immune-medi... | Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune and systemic inflammatory diseases. This compound is effective in a wide range of clinical conditions other than primary immunodeficiency, including autoimmune diseases, inflammatory disorders, infections, organ transplantation, and possibly supportive therapy for cancer. Systemic corticosteroids remain the gold standard treatment for many autoimmune diseases, but their long-term use is associated with complications in diverse organs and systems. Osteoporosis, osteonecrosis, cardiovascular disease, infections, and cancer have been associated with this treatment. Therefore, physicians are occasionally forced to withdraw the treatment with steroids. Biological agents may represent a good alternative, but in addition to being very expensive, these agents may have serious side effects. This review aimed to cover the major advances in the use of IVIg as a steroid-sparing agent in some relevant autoimmune diseases. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,739 |
Although gender and oestrogen treatment influence production of the vasorelaxant, NO, their influence on factors downstream in the NO signal-transduction pathway, specifically protein kinase G (PKG), remains unknown. We aimed to study the influence of sex hormones on PKG, along with the endothelial modulation of these effects, in rat thoracic aortic rings in two separate groups, control male and female rats and ovariectomized female rats after treatment with oestrogen or vehicle. Vessel preparations were preconstricted with phenylephrine (0.1 microM). Constrictions were greater in male than female aortas. This differential effect was attenuated by endothelium removal, addition of the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 microM) and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100 microM), supporting the role of NO in maintenance of basal relaxation and vascular tone in females. We have examined the relative activity of the specific PKG subtypes 1 alpha and 1 beta in vascular smooth muscle, based on relaxation of rat aortas by two cGMP analogues with different selectivity, beta-phenyl-l-N(2)-ethano-8-bromo-cGMP (8-Br-PET-cGMP) and 8-(2-aminophenylthio)cGMP (8-APT-cGMP). 8-Br-PET-cGMP was more potent than 8-APT-cGMP in both sexes, suggesting that PKG 1 alpha is the primary subtype involved in vasorelaxation. The gender differences in PKG activity were examined based on relaxation responses in male and female rat aortas. Both 8-Br-PET-cGMP and 8-APT-cGMP were more potent in aortas from male than female rats. In further studies on the endothelial modulation of relaxation with 8-APT-cGMP, the differential gender-vasorelaxation response was negated by endothelium removal and addition of the guanylate cyclase inhibitor ODQ (1 microM), but not by the NOS inhibitor L-NMMA (100 microM), suggesting that an endothelial-dependent factor other than NO may be responsible for the observed differential PKG-mediated vasorelaxation between the sexes. To further investigate oestrogen influence on PKG, treated female rats were studied. Contrary to our hypothesis, in the presence of 1 microM ODQ, there were no differences in either the phenylephrine constriction, or the relaxation with 8-APT-cGMP from either sham-operated, vehicle-treated or oestrogen-treated ovariectomized rats. In conclusion, female rat aortas have greater basal NO production compared with males. Relaxant responses to PKG activation are greater in aortas from male compared with female rats. These findings suggest hormonal regulation of PKG; however, oestrogen treatment of ovariectomized rats did not affect PKG activity, suggesting factors other than oestrogen may be responsible for the gender differences noted in this study. | This study examines the downstream NO release pathway and the contribution of different vasodilator mediators in the acetylcholine-induced response in rat aorta 5-months after the loss of ovarian function. Aortic segments from ovariectomized and control female Sprague-Dawley rats were used to measure: the levels of superoxide anion, the superoxide dismutases (SODs) activity, the cGMP formation, the cGMP-dependent protein kinase (PKG) activity and the involvement of NO, cGMP, hydrogen peroxide and hyperpolarizing mechanisms in the ACh-induced relaxation. The results showed that ovariectomy did not alter ACh-induced relaxation; incubation with L-NAME, a NO synthase inhibitor, decreased the ACh-induced response to a lesser extent in aorta from ovariectomized than from control rats, while ODQ, a guanylate cyclase inhibitor, decreased that response to a similar extent; the blockade of hyperpolarizing mechanisms, by precontracting arteries with KCl, decreased the ACh-induced response to a greater extent in aortas from ovariectomized than those from control rats; catalase, that decomposes hydrogen peroxide, decreased the ACh-induced response only in aorta from ovariectomized rats. In addition, ovariectomy increased superoxide anion levels and SODs activity, decreased cGMP formation and increased PKG activity. Despite the increased superoxide anion and decreased cGMP in aorta from ovariectomized rats, ACh-induced relaxation is maintained by the existence of hyperpolarizing mechanisms in which hydrogen peroxide participates. The greater contribution of hydrogen peroxide in ACh-induced relaxation is due to increased SOD activity, in an attempt to compensate for increased superoxide anion formation. Increased PKG activity could represent a redundant mechanism to ensure vasodilator function in the aorta of ovariectomized rats. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,740 |
Recent clinical trials indicate that the severity of diabetic neuropathy is correlated with the level of patient glycemic control. In the current study, hyperglycemia induces apoptotic changes in dorsal root ganglion neurons and Schwann cells in vivo both in streptozotocin-treated diabetic rats and in rats made acutely hyperglycemic with infused glucose. Typical apoptotic nuclear and cytoplasmic changes are observed. In addition mitochondrial changes recently reported to occur as part of the apoptotic cascade, such as ballooning of mitochondria and disruption of the internal cristae, are seen in diabetic dorsal root ganglion neurons and Schwann cells. Similar changes have been reported in neurons in the presence of oxidative stress. In order to study the neurotoxic effects of high glucose we developed an in vitro model using rat dorsal root ganglion neurons. In dorsal root ganglion cultured in defined medium, addition of moderate glucose levels results in neurite degeneration and apoptosis. These changes are coupled with activation of caspase-3, dependent on the concentration of glucose. The apoptotic changes observed in vitro are similar to those observed in vivo. In contrast, addition of IGF-I, even at physiological concentrations, prevents activation of caspase-3 and neuronal apoptosis in vitro. We suggest that oxidative stress may promote the mitochondrial changes in diabetic animals and lead to activation of programmed cell death caspase pathways. These results imply a new pathogenetic mechanism for diabetic sensory neuropathy. | Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,741 |
Endothelial dysfunction is involved in the various stages of cardiovascular (CV) disease development. Microparticles (MPs) originated from endothelial cells as biological markers of endothelial injury and repair could appear sufficient predictor of clinical outcomes and probable they might use in biomarker-guided therapy. Apoptotic endothelial cell-derived MPs are able to directly mediate a microvascular inflammation and worsening of endothelial integrity. In contrast, endothelial MPs originated from activated endothelial cells might contribute vascular repair and vasodilatation. It has been suggested that endothelial cells release phenotypically and quantitatively distinct endothelial MPs in activation and apoptosis, and that the phenotype of MP pattern can provide useful information reflecting the nature of endothelial injury. Editorial comment is discussed the role of impaired immune pattern of circulating endothelial cell-derived MPs as a personalized marker of vascular remodelling or endothelial dysfunction among CV disease persons. | ABSTRACT ::: Vascular illness is an obsessive condition of expansive and medium solid corridors and is activated by endothelial cell dysfunction. treatment of vascular diseases include, smoking and drinking should be controlled, lowering of blood pressure, glucose levels and cholesterol, and regular exercise should be done, vascular disease usually happens at destinations of turbulent blood stream, for example, when the course of blood stream in the corridors changes suddenly. Drugs can be recommended by your specialist to lower cholesterol levels, to diminish or control hypertension, to enhance blood stream, and to control glucose in diabetes. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,742 |
The aim of this study was to compare serum 17β-estradiol of menopausal women with/without Oral Dryness (OD) feeling, and evaluate the re-lationship between serum 17β-estradiol and severity of OD feeling. A case-control study was carried out on 70 selected menopausal women aged 40 - 77 years with or without OD feeling (35 as case, 35 as control) conducted at the Clinic of Oral Medicine, Tehran University of Medical Sciences. Xerostomia inventory (XI) score was used as an index of OD feeling severity. The serum 17β-estradiol concentration was measured by an enzyme immunoassay kit (ELISA). Statistical analysis of Student’s t-test and Spearman correlation coefficient was used. The mean serum concentration of 17β-estradiol was significantly lower in case than control. There was a significant negative correlation between XI score and concentration of 17β-estradiol in menopausal women (r = –0.311, P = 0.004). It seems that there is a negatively slight correlation between OD feeling severity and serum 17β-estradiol in menopausal women. | Numerous symptoms can be attributed to the lack of oestrogen at the time of the menopause. Some of the mechanisms for this are still unclear. However, while there is substantial evidence that many of the symptoms that women encounter during the menopausal period can be directly attributed to oestrogen deficiency, others are less well supported. An up-to-date review of the literature is provided. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,743 |
OBJECTIVE ::: Coumarin, used in the treatment of chronic venous diseases, is mainly metabolized to non-toxic 7-hydroxy-coumarin by CYP2A6. At least, 3 variant alleles, CYP2A6*2, CYP2A6*3 and CYP2A6*4A, have been shown to encode catalytically defective proteins. Sporadic elevation of liver enzymes has been reported on the chronic administration ofcoumarin. We sought to determine if susceptibility to coumarin-associated liver dysfunction is genetically determined by polymorphism in CYP2A6 and impairment of the 7-hydroxylation ofcoumarin. Additionally, we were interested in the effect of polymorphism on smoking because of the predominant role of CYP2A6 in the metabolism of nicotine. ::: ::: ::: METHODS ::: The investigation was performed prospectively within a randomized double-blind clinical trial of the coumarin-containing drug SB-LOT (90 mg coumarin + 540 mg troxerutin/d) vs. placebo in 231 German patients with chronic venous insufficiency. Monitoring of the hepatic status involved regular measurements of liver function during the 16-week treatment. Genotyping of CYP2A6 was carried out by means of PCR and confirmed by DNA sequencing analysis. ::: ::: ::: RESULTS ::: The allelic frequencies of the variant CYP2A6*2 and CYP2A6*3 alleles were 0.023 and 0.014, respectively. There was no significant difference in the incidence of liver dysfunction between heterozygotes with CYP2A6*2, CYP2A6*3 and wild-type homozygotes. CYP2A6 polymorphism had no significant effect on smoking behavior. ::: ::: ::: CONCLUSION ::: No evidence was obtained that the studied polymorphism in CYP2A6 is a determinant of the coumarin-associated liver dysfunction. | Previous studies on healthy subjects have shown that the intake of 6 g Cinnamomum cassia reduces postprandial glucose and that the intake of 3 g C. cassia reduces insulin response, without affecting postprandial glucose concentrations. Coumarin, which may damage the liver, is present in C. cassia, but not in Cinnamomum zeylanicum. The aim of the present study was to study the effect of C. zeylanicum on postprandial concentrations of plasma glucose, insulin, glycaemic index (GI) and insulinaemic index (GII) in subjects with impaired glucose tolerance (IGT). A total of ten subjects with IGT were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with placebo or C. zeylanicum capsules. Finger-prick capillary blood samples were taken for glucose measurements and venous blood for insulin measurements, before and at 15, 30, 45, 60, 90, 120, 150 and 180 min after the start of the OGTT. The ingestion of 6 g C. zeylanicum had no significant effect on glucose level, insulin response, GI or GII. Ingestion of C. zeylanicum does not affect postprandial plasma glucose or insulin levels in human subjects. The Federal Institute for Risk Assessment in Europe has suggested the replacement of C. cassia by C. zeylanicum or the use of aqueous extracts of C. cassia to lower coumarin exposure. However, the positive effects seen with C. cassia in subjects with poor glycaemic control would then be lost. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,744 |
A liquid chromatographic assay was used to determine the choline and acetylcholine concentrations in the four chambers of rat hearts 2, 4, and 8 days after transplantation into an abdominal site. Corresponding measurements were made in the hearts of host rats. We found regional cardiac acetylcholine concentrations in controls follow the nonuniform pattern seen with choline acetyltransferase (CAT) activity, being highest in the atria (8-12 nmol/g) and lower in the ventricles (0.7-1.6 nmol/g). Following transplantation, acetylcholine levels decreased significantly only in the right ventricle after 8 days. Following a unilateral vagotomy (random, left or right), acetylcholine concentrations in the distal portion of the severed nerve decreased to half the value of the intact contralateral side by 4 days. The continued presence of acetylcholine, despite significantly reduced CAT activity in the severed nerve and transplanted heart, suggests that acetylcholine is preserved, perhaps by vesiculation in nonstimulated postganglionic terminals. The localized decrease in acetylcholine in the right ventricle after 8 days suggests that transplantation may interrupt the postganglionic fibers to this area. | BACKGROUND ::: Patients with familial amyloid polyneuropathy, a rare hereditary form of amyloidosis, have progressive autonomic neuropathy. The disease usually does not induce heart failure but is associated with sudden death, conduction disturbances, and an increased risk of complications during anesthesia. Although cardiac sympathetic denervation has been clearly demonstrated, the postsynaptic status of the cardiac autonomic nervous system remains unelucidated. ::: ::: ::: METHODS AND RESULTS ::: Twenty-one patients were studied (age, 39+/-11 years; normal coronary arteries; left ventricular ejection fraction 68+/-9%). To evaluate the density and affinity constants of myocardial muscarinic receptors, PET with (11)C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, was used. Cardiac beta-receptor functional efficiency was studied by the heart rate (HR) response to intravenous infusion of isoproterenol (5 minutes after 2 mg of atropine, 5, 10, and 15 ng/kg per minute during 5 minutes per step). The mean muscarinic receptor density was higher in patients than in control subjects (B'(max), 35.5+/-8.9 versus 26.1+/-6.7 pmol/mL, P=0.003), without change in receptor affinity. The increase in HR after injection of atropine as well as of MQNB was lower in patients compared with control subjects despite a similar basal HR (DeltaHR after atropine, 11+/-21% versus 62+/-17%; P<0.001), consistent with parasympathetic denervation. Incremental infusion of isoproterenol induced a similar increase in HR in patients and control subjects. ::: ::: ::: CONCLUSIONS ::: Cardiac autonomic denervation in familial amyloid polyneuropathy results in an upregulation of myocardial muscarinic receptors but without change in cardiac beta-receptor responsiveness to catecholamines. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,745 |
Background: Three randomized Phase III trials (E2100, AVADO, and RIBBON-1) in patients with MBC have demonstrated that combining BV with first-line chemotherapy (taxane-, anthracycline-, or capecitabine-based) improves progression-free survival (PFS). We present a metaanalysis of patients with TNBC treated in the first-line setting. Methods: Kaplan-Meier methodology was used to estimate the median duration of PFS and overall survival (OS). Unstratified and stratified log-rank tests were used to assess the difference in PFS and OS between treatment cohorts (chemo only vs chemo+BV). For AVADO, only the 15 mg/kg BV group was included. Unstratified and stratified hazard ratios (HRs) were estimated using the Cox regression model. In the stratified analysis, disease-free interval, number of metastatic sites, visceral involvement (liver and/or lung), and the study were included as stratification factors. 1-year survival rates were compared using normal approximation method (Greenwood estimate for standard error). All p-values were two-sided and the type I error rate was set to 0.05 with no multiplicity adjustment. 95% confidence intervals (CIs) were calculated. Results: 621 patients were included in the pooled analysis: 258 in the chemo-only cohort and 363 in the chemo+BV cohort. Baseline characteristics in the two cohorts were similar. Median PFS was 5.4 months with chemo alone vs 8.1 months with chemo+BV (unstratified HR=0.65, 95% CI: 0.54-0.78, log-rank P Conclusions: The meta-analysis of patients with TNBC treated in the first-line Phase III trials of BV showed a statistically significant 35% decrease in the risk of disease progression or death (unstratified analysis) and a statistically significant 19% improvement in response rate. There was no difference in OS. The safety profile in this subgroup of patients is consistent with that observed in multiple Phase III studies across a variety of tumor types. Citation Information: Cancer Res 2010;70(24 Suppl):nr P6-12-03. | TNBC (Triple Negative Breast Cancer) is a subtype of breast cancer with an aggressive phenotype which shows high metastatic capability and poor prognosis. Owing to its intrinsic properties like heterogeneity, lack of hormonal receptors and aggressive phenotype leave chemotherapy as a mainstay for the treatment of TNBC. Various studies have demonstrated that chemotherapy alone or therapeutic drugs targeting TNBC pathways, epigenetic mechanisms and immunotherapy alone have not shown significant improvement in TNBC patients. On the other hand, a combination of therapeutic drugs or addition of chemotherapy with therapeutic drugs has shown substantial improvement in results and proven to be an effective strategy for TNBC treatment. This review sheds light on effective combinational drug strategies and current clinical trial status of various combinatorial drugs for the treatment of TNBC. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,746 |
Ethnopharmacological relevance Low molecular weight fucoidan (LMWF), extracted from Laminaria japonica Areschoug, is a traditional Chinese medicine, commonly used to alleviate edema, particularly for feet with numbness and pain. Aim of the study Diabetic mellitus (DM) patients are at high risk of developing peripheral arterial disease (PAD). Individuals with DM and PAD co-morbidity have a much higher risk of critical limb ischemia. LMWF showed several beneficial effects, such as anti-inflammation, anti-thrombosis, and enhancing revascularization. Therefore, we hypothesized that LMWF might be beneficial to diabetes-induced PAD, and investigated the therapeutic potential of LMWF on diabetic PAD rats. Materials and methods Type 2 diabetic Goto-Kakizaki (GK) rats were made PAD by injection of sodium laurate into femoral artery. LMWF (20, 40 or 80 mg/kg/day) or cilostazol (100 mg/kg/day) were given to diabetic PAD rats for 4 weeks, respectively. The effects of LMWF on foot ulceration and claudication, plantar blood flow, collateral vessel formation, endothelium morphology, gastrocnemius injury, platelet aggregation, vessel vasodilation, and the expressions of inflammation factors, VEGF, eNOS, and nitric oxide were measured. Results We found that LMWF markedly ameliorated foot ulceration and claudication, and improved the plantar perfusion by reversing hyperreactive platelet aggregation, ameliorating endothelium-dependent vasodilation and revascularization on diabetic PAD rats. In addition, upregulation of several inflammatory factors, such as ICAM-1 and IL-1β in the gastrocnemius muscles of ischemic hindlimb were suppressed by LMWF administration. And eNOS phosphorylation at Ser1177 and NO production were significantly enhanced in LMWF-treated diabetic PAD rats. Conclusions Taken together, our findings demonstrated that LMWF exhibits therapeutic effect on hindlimb ischemia in type 2 diabetic rats likely through ameliorating endothelium eNOS dysfunction and enhancing revascularization, thus, providing a potential supplementary non-invasive treatment for diabetes-induced PAD. | BACKGROUND ::: Diabetes mellitus (DM) complications are associated with ischemic injury. Angiogenesis is a therapeutic strategy for diabetic foot. The aim of this study was to investigate the possible angiogenic effect of low molecular weight fucoidan (LMWF) in diabetic peripheral arterial disease (PAD). ::: ::: ::: METHODS ::: Diabetic db/db mice and age-matched C57BL/6 mice underwent femoral artery ligation followed by LMWF (30, 60, 80 mg/kg per day, p.o.) or cilostazol (30 mg/kg/day, p.o.) treatment for 6 weeks. Endothelium-dependent vasodilation and blood flow of the hindlimb were measured. Histological and western blot analyses of CD34, vascular endothelial growth factor (VEGF), eNOS, and inflammatory factors in the gastrocnemius were performed. The effects of LMWF were confirmed in human umbilical vein endothelial cells (HUVEC). ::: ::: ::: RESULTS ::: Diabetic mice with ligation exhibited hindlimb ulceration, hydrosarca, and necrosis, increased expression of inflammatory factors, and decreased levels of VEGF and eNOS phosphorylation. Treatment with LMWF markedly ameliorated foot lesions, suppressed expression of inflammatory factors, and improved plantar perfusion by promoting endothelium-dependent vasodilation and revascularization in diabetic PAD mice. In high-glucose treated HUVEC, LMWF (40 μg/mL) reversed blunted endothelial cell proliferation, migration, and tube formation, and promoted eNOS phosphorylation and VEGF expression, whereas HUVEC pretreatment with 100 μmol/L NG -nitro-l-arginine methyl ester, an eNOS antagonist, markedly inhibited the effects of LMWF. ::: ::: ::: CONCLUSION ::: This study demonstrates that LMWF alleviates hindlimb ischemic damage, at least in part by promoting eNOS phosphorylation, nitric oxide production, and VEGF expression, resulting in enhanced angiogenesis in the ischemic region. | BACKGROUND ::: Diabetes mellitus (DM) complications are associated with ischemic injury. Angiogenesis is a therapeutic strategy for diabetic foot. The aim of this study was to investigate the possible angiogenic effect of low molecular weight fucoidan (LMWF) in diabetic peripheral arterial disease (PAD). ::: ::: ::: METHODS ::: Diabetic db/db mice and age-matched C57BL/6 mice underwent femoral artery ligation followed by LMWF (30, 60, 80 mg/kg per day, p.o.) or cilostazol (30 mg/kg/day, p.o.) treatment for 6 weeks. Endothelium-dependent vasodilation and blood flow of the hindlimb were measured. Histological and western blot analyses of CD34, vascular endothelial growth factor (VEGF), eNOS, and inflammatory factors in the gastrocnemius were performed. The effects of LMWF were confirmed in human umbilical vein endothelial cells (HUVEC). ::: ::: ::: RESULTS ::: Diabetic mice with ligation exhibited hindlimb ulceration, hydrosarca, and necrosis, increased expression of inflammatory factors, and decreased levels of VEGF and eNOS phosphorylation. Treatment with LMWF markedly ameliorated foot lesions, suppressed expression of inflammatory factors, and improved plantar perfusion by promoting endothelium-dependent vasodilation and revascularization in diabetic PAD mice. In high-glucose treated HUVEC, LMWF (40 μg/mL) reversed blunted endothelial cell proliferation, migration, and tube formation, and promoted eNOS phosphorylation and VEGF expression, whereas HUVEC pretreatment with 100 μmol/L NG -nitro-l-arginine methyl ester, an eNOS antagonist, markedly inhibited the effects of LMWF. ::: ::: ::: CONCLUSION ::: This study demonstrates that LMWF alleviates hindlimb ischemic damage, at least in part by promoting eNOS phosphorylation, nitric oxide production, and VEGF expression, resulting in enhanced angiogenesis in the ischemic region. | eng_Latn | 22,747 |
We studied the plasma levels and systemic anticholinergic activity of tropicamide after ocular administration in eight women. Two 40 microliters drops of 0.5% tropicamide were instilled into the lower cul-de-sac of one eye of the subjects and concentrations and respective muscarinic receptor occupancy of tropicamide in plasma were monitored using radioligand binding techniques. Tropicamide was rapidly absorbed systemically with the mean peak concentration in plasma being 2.8 +/- 1.7 ng/ml (mean +/- SD) at five minutes after instillation. Tropicamide disappeared rapidly from the systemic circulation: drug concentration in plasma was 0.46 +/- 0.51 ng/ml (mean +/- SD) at 60 minutes and below 240 pg/ml at 120 minutes after instillation. Tropicamide bound to muscarinic receptors of rat brain with an apparent equilibrium binding constant (Ki-value in plasma) 220 +/- 25 nM (mean +/- SD, n = 3). Tropicamide occupied maximally 8% of muscarinic receptors in plasma after ocular application. The low affinity of tropicamide for muscarinic receptors and its negligible receptor occupancy in plasma can explain the low incidence of systemic side-effects of tropicamide eyedrops. | OBJECTIVE ::: To determine the effects of topical 0.5% tropicamide on anterior segment morphology (ASM) and intraocular pressure (IOP) in normal and glaucomatous cats. ANIMALS USED: Normal cats and cats with inherited primary congenital glaucoma (PCG). ::: ::: ::: PROCEDURES ::: Control IOP curves were performed in untreated normal and PCG cats. In the first experiment, tropicamide was applied OD in eight normal and nine PCG cats. IOP and pupillary diameter (PD) were measured at 0, 30, and 60 min, then hourly until 8 h post-treatment. In a second experiment, six normal and seven PCG cats received tropicamide OD. High-resolution ultrasound images were obtained at 0, 1, 5, and 10 h post-treatment to measure ASM changes. IOP and PD were measured OD at 0, 1, 2, 3, 5, 7, and 9 h. ::: ::: ::: RESULTS ::: In untreated normal cats IOP OU decreased throughout the day. In PCG cats IOP OU had wide fluctuations over time. In normal cats IOP response varied in the treated eye but did not change significantly in untreated eyes. IOP significantly increased from baseline in both eyes of all treated PCG cats. Increases in IOP were associated with some ASM changes. Cats with PCG had a significantly smaller angle recess areas, diminished ciliary clefts and decreased iris-lens contact. ASM changes were not strongly correlated with IOP in all cats. ::: ::: ::: CONCLUSIONS ::: The ASM of PCG cats is markedly different from normal cats, and clinically significant increases in IOP OU occur in cats with PCG after tropicamide treatment. The mechanism for this increase remains unclear. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,748 |
In the European multicenter trial 246 female patients with suspicious mammographic result and/or breast mass were studied. In 253 lesions (195 palpable, 58 non-palpable) 165 malignant and 88 benign results were obtained histologically. All scans were evaluated centrally and institutionally. Central evaluation (per lesion) resulted in a sensitivity of 71% and a specificity of 69%. For palpable lesions, sensitivity was 83% in the central read and 91% in the institutional read. No difference was observed between invasive ductal and invasive lobular carcinoma. X-ray density had no influence on scintigraphic sensitivity. Sensitivity and specificity of mammography were 91% and 42%, respectively. | The search for new radiopharmaceuticals for tumour diagnosis usually proceeds on the basis of rational concepts drawing on the latest advances in molecular biology. Using this approach, radioactive peptide hormones, antibodies and oligonucleotides have been developed that are used increasingly in nuclear medicine for diagnostic and therapeutic purposes. This article, however, focusses on a group of radiopharmaceuticals whose use in tumour diagnosis was not the outcome of a methodical development programme but rather the result of a chance discovery. These radiopharmaceuticals, thallium-201 and technetium-99m labelled 2-methoxyisobutylisonitrile (MIBI), tetrofosmin and furifosmin, were first developed through extensive research efforts for cardiac imaging, but during their worldwide application for myocardial scintigraphy they were accidentally found to accumulate in tumours. Intensive studies were then begun on cell cultures in an attempt to discover the cause of their uptake into tumours. The aim was to compare the effectiveness of the radiopharmaceuticals for tumour diagnosis in a range of indications and to investigate the various mechanisms by which they are taken up into tumours. While the more favourable radiophysical properties of 99mTc-MIBI render it superior to 201Tl for many diagnostic purposes, neither 99mTc-tetrofosmin nor 99mTc-furifosmin has yet proved suitable for clinical routine examinations, although the former has found limited application. In the case of 99mTc complexes, the breakthrough came with the experimental finding that these substances are substrates of P-glycoprotein, a product of the human multidrug resistance gene (MDR1). The concentration of 99mTc complexes in tumour cells is a function of a passive, membrane potential-dependent influx into and a P-glycoprotein-controlled efflux out of the tumour cell. Preliminary studies suggest that in vivo detection of MDR may even be possible. There is also evidence that the P-glycoprotein-mediated transport system can be blocked competitively. However, it will be some time before a system can be developed for detection of MDR on a routine basis. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,749 |
BACKGROUND AND PURPOSE ::: The primary objective of this study was to establish in vivo the relationship between 2-2-nitro-1H-imidazol-1yl-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) adduct formation and intratumoral oxygen concentrations measured by electron paramagnetic resonance (EPR) in a tumor model mimicking a clinical situation. The secondary objective was an attempt to calibrate in situ the immunofluorescence (IF) signal with EPR oximetry. ::: ::: ::: MATERIALS AND METHODS ::: IM syngeneic fibrosarcoma (NFSA) bearing C3H mice were used. Three days after injection of a paramagnetic charcoal into the tumor, the mice were anesthetized, injected with the hypoxic marker EF5, and monitored every 20 min for 3 h with a low-frequency EPR spectrometer. Animals were allowed to breath either under 21 or 100% O(2). Tumors were then harvested, frozen, cut into sections including the charcoal and processed for EF5 adducts detection using monoclonal antibodies. Slices were viewed with a fluorescence microscope and 190x140 micrometer areas surrounding the charcoal were digitized and analyzed with the NIH-Image and Adobe Photoshop software. The fluorescence intensity (FI) was measured in the whole pictures and in strips of 10 micrometer around the charcoal. ::: ::: ::: RESULTS ::: EF5 binding increased with decreasing pO(2), most substantially at pO(2) below 5 mm Hg. Baseline (ambient air) pO(2) reached 3.2+/-2.1 mm Hg in NFSA tumors. It increased to 9.8+/-3.2 mm Hg under 100% O(2). A statistically significant correlation was observed on an individual tumor basis between the FI in the first 10 micrometer strip around the charcoal and the pO(2) determined by EPR oximetry (Wilcoxon signed rank test: P<0.001). ::: ::: ::: CONCLUSIONS ::: The present study confirms the intrinsic relationship between EF5 adduct binding and intratumoral pO(2) in an in vivo environment under biologically-relevant pO(2) values of less than 10 mm Hg. | Purpose: The purpose of this study was to assess the presence of tumor hypoxia using two independent techniques: binding of the 2-nitroimidazole EF5 and Eppendorf needle electrode measurements. The distribution of tumor hypoxia was assessed with respect to tumor necrosis in corresponding histological studies. Methods and Materials: Each of several rats bearing a subcutaneous 9L glioma or Morris 7777 hepatoma tumor was given EF5 i.v. to a final, whole-body concentration of 100 μM. About 2.5 h later, each rat was anesthetized, and needle electrode measurements were made in the tumor along 1–5 tracks (30–200 individual measurements). At 3 h post-EF5 injection, the tumor was excised and frozen. Frozen sections were analyzed for the presence and distribution of binding of EF5 and necrosis using immunohistochemical techniques followed by staining with hematoxylin and eosin (H&E). The histochemical analysis and electrode readings in similar regions of the tumor were compared. Results: Electrode measurements were taken at 0.4-mm intervals along one-dimensional tracks, whereas EF5 binding measurements from tissue sections contained two-dimensional information at high spatial resolution (∼2.5 μ). The EF5 measurements showed greater spatial heterogeneity than did the electrode measurements. In tumor regions with minimal necrosis, needle tracks with relatively high pO 2 readings were usually found to contain relatively low EF5 binding, and vice versa. Because EF5 binding is inversely related to tissue pO 2 , this result was expected. The expected inverse correlation of the two techniques was most disparate in necrotic tumor regions (confirmed by H&E staining), where needle electrode measurements showed low to zero pO 2 values, but little or no EF5 binding was found. Conclusion: The two methods compared in this study operate in fundamentally different ways and provide substantially different information. EF5 binding provided detailed spatial information on the distribution of hypoxia in viable tumor tissue. There was no EF5 binding in necrotic tumor tissue because cells in such tissue were unable to metabolize the drug. In contrast, output from the needle electrode method appeared to represent a “track-average” tissue pO 2 and did not distinguish between extreme hypoxia and either macroscopic or microscopic necrosis. At the present time, the importance of tumor necrosis in determining treatment response is unknown. However, our data suggest that the Eppendorf needle electrode technique will overestimate the presence of hypoxia. Both techniques are potentially limited by sampling errors in tumors with heterogeneous distributions of hypoxia. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,750 |
Objectives ::: The present study aimed to clarify the reliabilities of four characteristic appearances, subchondral cyst, erosion, generalized sclerosis, and osteophyte, for evaluation of degenerative diseases with osseous changes in the temporomandibular joint (TMJ) using panoramic TMJ projection imaging and computed tomography (CT), and to investigate the imaging features of these modalities for subchondral cyst with reference to its magnetic resonance imaging (MRI) features. | A comprehensive study of femoral heads of patients and cadavers with osteoarthritis, rheumatoid arthritis, osteonecrosis, and calcium pyrophosphate dihydrate deposition disease allows insight into the radiographic and pathologic appearance of subchondral radiolucencies in these disorders. The term geode, rather than cyst or pseudocyst, may be a more appropriate decription of these lesions. In osteoarthritis, goedes occur on the pressure segment of the femoral head in association with loss of articular space; in rheumatoid arthritis, they are initially noted at the chondro-osseous junction and subsequently involve the entire femoral head. In osteonecrosis, geodes appear in the necrotic segment of the femoral head. In calcium pyrophosphate deposition disease, geodes resemble those in osteoarthritis but are larger, more numerous, and more widespread. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,751 |
Background and Purpose: Irradiation of ocular pterygium is considered a valuable treatment supplementation after surgical therapy. Since prospective randomized trials are scare and only limited patient data are available, the aim of this study was to evaluate the patient population treated with fractioned 90 Sr irradiation after surgical pterygium resection. Patients and Methods: Between September 1993 and March 2001, 1,147 patients with pterygium lesions (1,320 lesions) were treated surgically and with 90 Sr postoperative β-irradiation. A total dose of 30 Gy was used for patients treated within 48 h after surgery, while those treated > 48 h postoperatively received a total dose of 35 Gy. A minimum follow-up period of 3 months was required for inclusion in the analysis, and 1,253 lesions were ultimately analyzed. Results: Recurrence of the pterygium after postoperative 90 Sr irradiation was observed in 97 of 1,253 cases (7.7%). Statistical analysis (uni- and multivariate) revealed, that male gender, younger age (< 40 years), prior treatment (surgery and radiotherapy) and immediate irradiation (< 2 h after surgery) were negative predictors for local recurrence. Temporary radiotherapy-induced side effects were observed in 15.2% of patients, including moderate conjunctivitis, local pain, visual disturbance and photophobia or an increase in tear flow. However, no long-term serious side effects were documented. Conclusion: 90 Sr irradiation of pterygium after surgery represents a safe and effective treatment option to prevent disease recurrence. The data obtained in this study indicate that a certain interval after surgery might improve therapy outcome. | PURPOSE ::: To investigate the effect of subconjunctival bevacizumab immediately after excision of primary pterygium. ::: ::: ::: METHODS ::: Eighty patients (80 eyes) with primary pterygium were included in this double-blind clinical trial. The pterygia were excised by the bare sclera technique. Then, the patients were randomized in 2 equal groups; group A received subconjunctival bevacizumab (1.25 mg/0.1 mL) injected immediately after surgical excision of the pterygium, and placebo was administered in the same way in group B. Patients were followed-up for 9 months after the operation, and the possible complications and recurrence rate were documented. Thirty-three patients (33 eyes) completed the study in each group. ::: ::: ::: RESULTS ::: The rate of complications was comparable between the 2 groups (57.6% in group A versus 63.6% in group B; P = 0.61). None of these complications was clinically significant, and they resolved spontaneously or by using conservative measures. The recurrence rate was higher in group B compared with group A (57.6% vs. 45.5%); however, this difference was not statistically significant (P = 0.33; odds ratio, 1.63; 95% confidence interval, 0.62-4.31). ::: ::: ::: CONCLUSIONS ::: Subconjunctival injection of bevacizumab immediately after surgical excision of primary pterygium is well-tolerated, but it cannot significantly prevent the recurrence of this condition. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,752 |
PURPOSE ::: To investigate if plasma cytokine concentrations predict a beneficial response to corticosteroid treatment in septic shock patients. ::: ::: ::: METHODS ::: A cohort of septic shock patients in whom a panel of 39 cytokines had been measured at baseline (n = 363) was included. Patients who received corticosteroids were propensity score matched to non-corticosteroid-treated patients. An optimal threshold to identify responders to corticosteroid treatment for each cytokine was defined as the concentration above which the odds ratio for 28-day survival between corticosteroid- and non-corticosteroid-treated patients was highest. ::: ::: ::: RESULTS ::: Propensity score matching partitioned 165 patients into 61 sets; each set contained matched corticosteroid- and non-corticosteroid-treated patients. For 13 plasma cytokines threshold concentrations were found where the odds ratio for survival between corticosteroid- and non-corticosteroid-treated patients was significant (P < 0.05). CD40 ligand was associated with the highest odds ratio and identified 21 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. Combinations of triplets of cytokines with a significant odds ratio, using the thresholds identified above, were tested to find a higher proportion of responders. IL3, IL6, and CCL4 identified 50 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. The odds ratio for 28-day survival was 19 (95 % CI 3.5-140, P = 0.02) with a concentration above threshold for a least one of these cytokines. ::: ::: ::: CONCLUSION ::: Plasma concentration of selected cytokines is a potential predictive biomarker to identify septic shock patients that may benefit from treatment with corticosteroids. | A prospective (Part I) and a retrospective (Part II) study were used to determine the safety and efficacy of corticosteroids in the treatment of septic shock. In Part I, 172 consecutive patients in septic shock admitted over an 8-year period were treated with either steroid or saline: 43 received dexamethasone (DMP), 43 received methylprednisolone (MPS), and 86 received saline. The study was double-blind and randomized, and the three groups were compared for age, severity of shock, presence of underlying disease, and year of study. In the 86 saline-treated patients, the mortality rate was 38.4% (33/86); in the steroid-treated patients, it was 10.4% (9/86). With MPS the mortality rate was 11.6% (5/43), and with DMP it was 9.3% (4/43). Thus, overall mortality was significantly less in the steroid-treated group than in the control group. Further, there was no significant difference in mortality rate between the DMP- and the MPS-treated patients. In Part II, 328 patients were studied retrospectively. One-hundred sixty were treated without steroid, and 168 were treated with either DMP or MPS. Again, the two groups of patients were compared for severity of shock, underlying disease, age, and year of study. Mortality among patients treated without steroid was 42.5% (68/160) and among patients treated with steroid was 14% (24/168); there was no significant difference in mortality rate between DMP- and MPS-treated patients. In Parts I and II combined, complications occurred in 6% of steroid-treated patients with no significant difference between DMP- and MPS-treated groups. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,753 |
REASONS FOR PERFORMING STUDY ::: The role of glucocorticoids (GCs) in the pathogenesis of laminitis is incompletely understood. Local tissue activity of GC is regulated by the steroid converting enzyme, 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD-1). Changes in integumentary (skin and hoof lamellar) 11beta-HSD activity occurring during laminitis could affect the extent to which GCs are involved in its development. ::: ::: ::: HYPOTHESIS ::: That changes in integumentary 11beta-HSD-1 activity associated with the laminitic condition would lead to elevated local tissue levels of GCs, which could subsequently contribute, through paracrine and autocrine mechanisms, to the further development of laminitis; and that similar changes in 11beta-HSD-1 activity would be evident in both skin and hoof lamellar tissue. ::: ::: ::: METHODS ::: Activity of 11beta-HSD-1 was determined in skin and hoof lamellar tissue specimens obtained from normal and laminitic horses using a radiometric assay. Skin samples were obtained from 10 normal horses and from 10 horses before and after induction of acute laminitis following administration of starch via nasogastric tube. Hoof lamellar samples were obtained from 10 normal horses, 10 horses following induction of acute laminitis and 4 chronically-foundered horses. Bidirectional 11beta-HSD-1 activity was measured in both skin and lamellar tissues. ::: ::: ::: RESULTS ::: 11-ketoreductase activity exceeded 11beta-dehydrogenase activity in both skin and lamellar tissues. Cutaneous activity was higher than lamellar 11beta-HSD-1 activity in all groups. Both ketoreductase and dehydrogenase activity increased in skin and lamellae following experimental induction of acute laminitis, but the increase in ketoreductase activity was substantially greater than that for dehydrogenase in the lamellae. Induction of acute laminitis was attended by increases of 227 and 220% in cutaneous dehydrogenase and ketoreductase activity, respectively, and 173 and 398% in lamellar dehydrogenase and ketoreductase activity, respectively (P<0.05). ::: ::: ::: CONCLUSIONS ::: The 11-ketoreductase moiety of 11beta-HSD-1 plays a role in equine skin and hoof lamellae regarding the regulation of local glucocorticoid activity. Increased 11-ketoreductase activity will lead to increased local tissue GC activity by virtue of conversion of cortisone to cortisol. ::: ::: ::: POTENTIAL RELEVANCE ::: The laminitic condition is attended by integumentary biochemical changes that enhance the local concentration of cortisol, especially in the hoof lamellar interface. Through multiple and diverse actions, increased local GC activity contributes to the pathogenesis and morbidity associated with laminitis. Pharmacological manipulation of 11beta-HSD-1 deserves further investigation regarding the prevention and treatment of laminitis. | Authors’ addresses: Department of Veterinary Medicine and Surgery, College of Veterinary Medi-cine, University of Missouri, Columbia, MO 65211 (Johnson, Messer); Department of BiomedicalSciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211 (Ganjam,Buff); Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Mis-souri, Columbia, MO 65211 (Turk, Wiedmeyer); and Department of Animal Science, College ofAgriculture, University of Missouri, Columbia, MO 65211 (Keisler); e-mail: [email protected](Johnson). © 2006 AAEP. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,754 |
ABSTRACTThe role of T-type calcium currents is rarely considered in the extensive literature covering the mechanisms of long-term synaptic plasticity. This situation reflects the lack of suitable T-type channel antagonists that till recently has hampered investigations of the functional roles of these channels. However, with the development of new pharmacological and genetic tools, a clear involvement of T-type channels in synaptic plasticity is starting to emerge. Here, we review a number of studies showing that T-type channels participate to numerous homo- and hetero-synaptic plasticity mechanisms that involve different molecular partners and both pre- and post-synaptic modifications. The existence of T-channel dependent and independent plasticity at the same synapse strongly suggests a subcellular localization of these channels and their partners that allows specific interactions. Moreover, we illustrate the functional importance of T-channel dependent synaptic plasticity in neocortex and thalamus. | The Federal Pain Research Strategy recommended development of nonopioid analgesics as a top priority in its strategic plan to address the significant public health crisis and individual burden of chronic pain faced by >100 million Americans. Motivated by this challenge, a natural product extracts library was screened and identified a plant extract that targets activity of voltage-gated calcium channels. This profile is of interest as a potential treatment for neuropathic pain. The active extract derived from the desert lavender plant native to southwestern United States, when subjected to bioassay-guided fractionation, afforded 3 compounds identified as pentacyclic triterpenoids, betulinic acid (BA), oleanolic acid, and ursolic acid. Betulinic acid inhibited depolarization-evoked calcium influx in dorsal root ganglion (DRG) neurons predominantly through targeting low-voltage–gated (Cav3 or T-type) and CaV2.2 (N-type) calcium channels. Voltage-clamp electrophysiology experiments revealed a reduction of Ca2+, but not Na+, currents in sensory neurons after BA exposure. Betulinic acid inhibited spontaneous excitatory postsynaptic currents and depolarization-evoked release of calcitonin gene–related peptide from lumbar spinal cord slices. Notably, BA did not engage human mu, delta, or kappa opioid receptors. Intrathecal administration of BA reversed mechanical allodynia in rat models of chemotherapy-induced peripheral neuropathy and HIV-associated peripheral sensory neuropathy as well as a mouse model of partial sciatic nerve ligation without effects on locomotion. The broad-spectrum biological and medicinal properties reported, including anti-HIV and anticancer activities of BA and its derivatives, position this plant-derived small molecule natural product as a potential nonopioid therapy for management of chronic pain. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,755 |
The term ‘dyslipidemia’ includes a wide family of lipoprotein metabolic defects often related to cardiovascular diseases. Despite the complexity of lipid disorders, current guidelines indicate LDL-C as the single most important therapeutic target; however, other lipido–proteic parameters, such as the concentration of lipoprotein subfractions (e.g., small-dense LDL) or their functional capacity (e.g., HDL reverse cholesterol transport), may display direct pro- or anti-atherogenic properties. Traditional lipid profiles may therefore be inadequate in representing dyslipidemia complexity and may prove to be ineffective in estimating the overall patient’s risk in this context. We designed a research project attempting to provide a coherent framework integrating traditional lipid profiling and advanced diagnostics, to assess qualitative and functional lipoprotein features in relevant clinical conditions and to correlate them with preclinical atherosclerosis. | Aims ::: Individuals with type 2 diabetes show shorter leukocyte telomere length (LTL) compared to people without diabetes. Reduced LTL is associated with increased carotid intima-media thickness (IMT) in healthy subjects. The aim of the study is to assess whether LTL also correlates with IMT in patients with diabetes. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,756 |
Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers. | Venous stasis ulcers (VSUs) represent both an enormous cost to the healthcare system and significant quality-of-life issue to patients. While certain high-technology products have shown promise, compression bandaging continues to be the gold standard of care. Recently, some regional Medicare carriers suggested that patients with VSUs should be able to perform self-bandaging in an effort to avoid reimbursing caregivers to provide this service. Using a database of 7251 patients from 29 wound care facilities maintained as part of an agreement under the Intellicure Research Consortium for users of Intellicure Inc's (The Woodlands, Tex) wound care software; activity of daily living (ADL) data was extracted for all patients with a VSU in whom this was collected (547 patients) to examine such an impact. Analysis showed that 55% of these patients required assistance with ADLs-the majority had issues with dressing and toileting. It is unlikely that patients who require assistance with dressing and toileting will be able to achieve adequate positioning to perform self-bandaging. Since it is possible that even patients who do not require assistance with ADLs might be unable to perform self-bandaging, the authors consider these results a conservative estimation. These results indicate that a significant number of patients are not capable of self-bandaging, thus placing their prognosis and quality-of-life at risk if they are unable to pay for the necessary professional services or do not have family members who are capable of bandaging. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,757 |
Patients who believe they have oral malodour often have a dry mouth condition instead. Here we have examined its relation to oral malodour, real or perceived. A direct relationship between the thickness of the film of residual saliva on mucosal surfaces throughout the mouth and perception of a dry mouth was observed. On the hard palate, the thickness of this film proved to be diagnostic for a dry mouth and corresponded to lower resting saliva flow and pH levels (P< 0.001). Intra-muscular administration of the anti-sialogogue, Robinul, accurately produced the dry mouth condition. Using a sulphide monitor, loss of volatile sulphur compounds into mouth air progressively occurred as the mouth became drier. Mouth pH and Eh on the dorsum of the tongue correspondingly fell. Mouth breathing led to tongue and palate moisture loss thus enabling escape of malodour volatiles into mouth air. Measurement of oral dryness should make it possible to differentiate genuine malodour from dry mouth related pseudo-malodour subjects, and in turn, the latter from patients that are halitophobic. This should facilitate identification of such patients and avoid error in their clinical management. | The purpose of this study based on a cross-sectional internet survey was to investigate the relationship between risk of obstructive sleep apnea (OSA) and self-assessed oral health status. The participants, who comprised individuals registered with an online research company, were required to complete a self-reported questionnaire. Those answering in the affirmative to both of the following two questions were placed in the OSA-risk group, while those answering in the negative were assigned to the control group: 'Have other people noticed pauses in your breathing while you are sleeping?' and 'Do you feel excessively sleepy during the daytime?'. A total of 493 were included in the OSA-risk group and 2,560 in the control group. Among the total 3,053 respondents, the highest prevalence for OSA risk in men was in the 50-59-year age range, although this tended to level off after age 60 years. No such trend was observed in women, however. Multiple logistic regression analysis was performed to identify the relationship between risk of OSA and self-assessed oral health status. Significant correlations were observed with the following parameters: difficulty in opening mouth (odds ratio [OR]: 2.66; 95% confidence interval [CI]: 1.647-4.311), dry mouth (OR: 2.11; CI: 1.544-2.876), bad breath (OR: 1.69; CI: 1.309-2.186), gingival bleeding (OR: 1.48; CI: 1.134-1.932), and gingival swelling (OR: 1.44; CI: 1.046-1.981). These results suggest a relationship between risk of OSA and self-assessed oral health status, indicating that treating OSA might improve oral health status. Further study is needed to demonstrate a causal relationship between OSA and self-assessed oral health status, however. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,758 |
OBJECTIVE ::: To determine whether duration of exposure to GH and/or rate of change of serum GH concentration are important factors in determining the growth rate of short children. ::: ::: ::: DESIGN ::: An analysis of parameters of occupancy percentage and rate of change of serum GH concentration was performed as part of a prospective study investigating the relationship between growth and GH in childhood. ::: ::: ::: PATIENTS ::: Sixty-four short prepubertal children (48 male, 16 female) aged between 4.7 and 11.9 years were studied. Thirty-one children were growing with a height velocity standard deviation score between 0 and -0.8 and were defined as short normal. Thirty-three children were growing with a height velocity standard deviation score less than -0.8 and were defined as short slowly growing. ::: ::: ::: MEASUREMENTS ::: Twenty-four hour serum GH concentration profiles were constructed by withdrawing samples at 20-minute intervals. Analysis of occupancy percentage was performed on each data array by determining cumulative distributions and plotting these as linear probits against log serum GH concentration. Estimates of peak (OC95), intermediate (OC50) and trough (OC5) occupancies were calculated. A first-order derivative of the concentration-time data array was determined for each profile as a measure of rate changes. ::: ::: ::: RESULTS ::: First-order derivative values were significantly greater in the short normal group than in the short slowly growing children (short normal median 1.41 mU/l/min; short slowly growing median 0.72 mU/l/min; P less than 0.001). OC95 values were significantly higher in the short normal group (median 19.31 mU/l) than the short slowly growing group (median 7.69 mU/l) (P less than 0.001). There was no difference in OC50 values. OC5 values were lower in short normal children (median 0.20 mU/l) than in the short slowly growing children (0.55 mU/l) (P less than 0.003). The most important factor in determining growth rate was the rate of change in serum GH concentration (FOD). Occupancy percentage played no part in the relationship. The regression equation was Height velocity SDS = 1.16 (In FOD) - 1.03; r = 0.75; P less than 0.001 ::: ::: ::: CONCLUSIONS ::: These data suggest that the pattern of presentation of GH in the circulation is an important factor in determining target organ response. Although occupancy percentages at differing serum GH concentrations differ between short slowly growing and short normal children, it is the rate of change of the hormone in the circulation which appears to be the more important 'signal' in terms of modulating growth. | In childhood, the largest secretory burst of GH occurs during nighttime, and consists of a complex mixture of molecular forms of GH that are thought to have different biologic activity. Standard GH assays cannot distinguish between bioactive and biologically inactive GH isoforms. To examine this relationship, overnight GH secretion was assessed by blood sampling every 30 min in 10 short prepubertal children (7 boys and 3 girls) to evaluate both the serum concentration and the biologic activity of GH. Serum GH concentrations were measured by an immunofluorometric assay and its biologic activity by the Nb2 cell bioassay. The 12-h (2000 h to 0800 h) and 6-h (2000 h to 0200 h and 0200 h to 0800 h) GH profiles were analyzed using the Pulsar program. When GH secretory pattern was measured by immunofluorometric assay, the area under the curve above the 0 line, the mean GH concentration, and the mean height of the secretory peaks were significantly higher during the first than during the second part of the night (29.17 ± 5.93 versus 16.29 ± 1.87 mIU/L, p < 0.05; 7.77 ± 1.28 versus 4.83 ± 0.33 mIU/L, p < 0.05; 4.61 ± 0.94 versus 2.68 ± 0.27 mIU/L, p < 0.05, respectively). In contrast, GH biologic activity was not significantly different during the two parts of the night. In conclusion, a dissociation between GH bioactivity and immunoreactivity is present in physiologic conditions, indicating that standard GH measurements do not provide any information on the biologic activity of the hormone. Although GH secretion is regulated by complex neuroendocrine mechanisms, the biologic activity of the hormone seems to be independent of them and is most probably regulated by peripheral mechanisms acting on its clearance or bioavailability to the target tissues. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,759 |
OBJECTIVES ::: We examined whether endogenous hydrogen peroxide (H2O2) is involved in pacing-induced metabolic vasodilation in vivo. ::: ::: ::: BACKGROUND ::: We have previously demonstrated that endothelium-derived H2O2 is an endothelium-derived hyperpolarizing factor in canine coronary microcirculation in vivo. However, the role of endogenous H2O2 in metabolic coronary vasodilation in vivo remains to be examined. ::: ::: ::: METHODS ::: Canine subepicardial small coronary arteries (> or =100 microm) and arterioles (<100 microm) were continuously observed by a microscope under cyclooxygenase blockade (ibuprofen, 12.5 mg/kg intravenous [IV]) (n = 60). Experiments were performed during paired right ventricular pacing under the following 7 conditions: control, nitric oxide (NO) synthase inhibitor (N(G)-monomethyl-L-arginine [L-NMMA], 2 micromol/min for 20 min intracoronary [IC]), catalase (a decomposer of H2O2, 40,000 U/kg IV and 240,000 U/kg/min for 10 min IC), 8-sulfophenyltheophylline (SPT) (an adenosine receptor blocker, 25 mug/kg/min for 5 min IC), L-NMMA+catalase, L-NMMA+tetraethylammonium (TEA) (K(Ca)-channel blocker, 10 microg/kg/min for 10 min IC), and L-NMMA+catalase+8-SPT. ::: ::: ::: RESULTS ::: Cardiac tachypacing (60 to 120 beats/min) caused coronary vasodilation in both-sized arteries under control conditions in response to the increase in myocardial oxygen consumption. The metabolic coronary vasodilation was decreased after L-NMMA in subepicardial small arteries with an increased fluorescent H2O2 production compared with catalase group, whereas catalase decreased the vasodilation of arterioles with an increased fluorescent NO production compared with the L-NMMA group, and 8-SPT also decreased the vasodilation of arterioles. Furthermore, the metabolic coronary vasodilation was markedly attenuated after L-NMMA+catalase, L-NMMA+TEA, and L-NMMA+catalase+8-SPT in both-sized arteries. ::: ::: ::: CONCLUSIONS ::: These results indicate that endogenous H2O2 plays an important role in pacing-induced metabolic coronary vasodilation in vivo. | We previously reported that combined blockade of adenosine receptors and ATP-sensitive K+ channels (K+(ATP) channels) blunted but did not abolish the response of coronary blood flow to exercise. This study tested the hypothesis that the residual increase in coronary flow in response to exercise after adenosine receptor and K+(ATP) channel blockade is dependent on endogenous NO. Dogs were studied at rest and during a four-stage treadmill exercise protocol under control conditions, during K+(ATP) channel blockade with glibenclamide (50 microg x kg(-1) x min(-1) i.c.) in the presence of adenosine receptor blockade with 8-phenyltheophylline (8-PT, 5 mg/kg i.v.), and after the addition of the NO synthase inhibitor N(G)-nitro-L-arginine (LNNA, 1.5 mg/kg i.c.). During control conditions, coronary blood flow was 49 +/- 3 mL/min at rest and increased to 92 +/- 8 mL/min at peak exercise. LNNA alone or in combination with 8-PT did not alter resting coronary flow and did not impair the normal increase in flow during exercise, indicating that when K+(ATP) channels are intact, neither NO nor adenosine-dependent mechanisms are obligatory for maintaining coronary blood flow. Combined K+(ATP) channel and adenosine blockade decreased resting coronary flow to 27 +/- 3 mL/min (P<.05), but exercise still increased flow to 45 +/- 5 mL/min (P<.05). The subsequent addition of LNNA further decreased resting coronary flow to 20 +/- 2 mL/min and markedly blunted exercise-induced coronary vasodilation (coronary vascular conductance, 0.20 +/- 0.03 mL x min(-1) x mm Hg(-1) at rest versus 0.24 +/- 0.04 mL x min(-1) x mm Hg(-1) during the heaviest level of exercise; P=.22), so that coronary flow both at rest and during exercise was below the control resting level. The findings suggest that K+(ATP) channels are critical for maintaining coronary vasodilation at rest and during exercise but that when K+(ATP) channels are blocked, both adenosine and NO act to increase coronary blood flow during exercise. In the presence of combined K+(ATP) channel blockade and adenosine receptor blockade, NO was able to produce approximately one quarter of the coronary vasodilation that occurred in response to exercise when all vasodilator systems were intact. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,760 |
BACKGROUND ::: The aim of this study was to analyze the impact of the induction chemoradiotherapy (IT) on the survival pattern in T3/T4-N0 non-small cell lung cancer (NSCLC) patients. ::: ::: ::: METHODS ::: The data of 71 patients treated from January 1992 to May 2007 were reviewed. Of these, 31 patients received IT prior to surgery (IT group: T3, 20 patients; and T4, 11 patients), and 40 directly underwent surgery (S group: T3, 34 patients; and T4, 6 patients). Survival rates were compared using the Kaplan-Meier analysis and the Cox proportional hazards models. ::: ::: ::: RESULTS ::: Mean ages were 62.5±9.9 years in the IT group and 67.7±7.1 in the S group. All patients but 1 completed the IT treatment and 27 patients (87%) were operated. A radical resection was possible in 21 patients (78%). In the IT group a complete pathologic response was obtained in 6 patients (22%), where 8 patients ended up in pI stage, 7 in pII stage, and 6 in pIII stage. The overall 5-year survival (long-term survival [LTS]) and disease-free 5-year survival (DFS) for the entire cohort were 40% and 34%, respectively. No significant differences were found when LTS in the IT group (44%) and in the S group (37%) were compared. At multivariate analysis, the completeness of resection was the only independent predictive factor (hazard ratio [HR]=5.18; 95% confidence interval [CI]=2.55 to 10.28) while Cox multivariate analysis (on the IT group only) confirmed the critical role of the pathologic downstaging (HR=4.62; 95% CI=1.54 to 13.89). ::: ::: ::: CONCLUSIONS ::: A multimodal strategy with IT treatment followed by surgery is a safe and reasonable treatment in T3/T4-N0 NSCLC patients, but no clear evidence of prognostic improvement may be assumed at the present time. Nevertheless, patients with radical resection and complete pathologic response have a very rewarding survival. | e18517 Background: In our study, we evaluated the survival results and prognostic factors among T4 local advanced non-small cell lung cancer (LA-NSCLC) patients in a large heterogeneous group, in accordance with the new staging system. Methods: We retrospectively evaluated the files of LA-NSCLC patients who have been treated at two centers between November 2003 and June 2012. One hundred twenty two T4 N0-3 M0 LA-NSCLC patients, identified according to the new staging system, were included in the study. Results: Median OS was 18.3 months, 1 year overall survival (OS) rate was 72%, 5 year OS rate was 28%. The median follow-up period was 17.4 months. Statistically significant predictors of survival were (p<0.20) ECOG-PS, age, subgroups of T4 factor, stage and primary treatment in OS univariate analysis. It was found that the statistically significant variables in multivariate analysis of OS rate were ECOG-PS (p=0.001), diagnostic stage (p=0.021), and primary treatment (p=0.004). In the group given non-curati... | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,761 |
Scavenger receptor SR-BI has been implicated in HDL-dependent atheroprotective mechanisms. We report the generation of an SR-BI conditional knockout mouse model in which SR-BI gene targeting by loxP site insertion produced a hypomorphic allele (hypomSR-BI). Attenuated SR-BI expression in hypomSR-BI mice resulted in 2-fold elevation in plasma total cholesterol (TC) levels. Cre-mediated SR-BI gene inactivation of the hypomorphic SR-BI allele in hepatocytes (hypomSR-BI-KO(liver)) was associated with high plasma TC concentrations, increased plasma free cholesterol/TC (FC/TC) ratio, and a lipoprotein-cholesterol profile typical of SR-BI-/- mice. Plasma TC levels were increased 2-fold in hypomSR-BI and control mice fed an atherogenic diet, whereas hypomSR-BI-KO(liver) and SR-BI-/- mice developed severe hypercholesterolemia due to accumulation of FC-rich, VLDL-sized particles. Atherosclerosis in hypomSR-BI mice was enhanced (2.5-fold) compared with that in controls, but to a much lower degree than in hypomSR-BI-KO(liver) (32-fold) and SR-BI-/- (48-fold) mice. The latter models did not differ in either plasma lipid levels or in the capacity of VLDL-sized lipoproteins to induce macrophage cholesterol loading. However, reduced atherosclerosis in hypomSR-BI-KO(liver) mice was associated with decreased lesional macrophage content as compared with that in SR-BI-/- mice. These data imply that, in addition to its major atheroprotective role in liver, SR-BI may exert an antiatherogenic role in extrahepatic tissues. | OBJECTIVE ::: Scavenger receptor class B type I (SR-BI) is a cell-surface HDL receptor that is implicated in reverse cholesterol transport and protection against atherosclerosis. We have previously demonstrated that SR-BI/apolipoprotein E double-knockout mice develop severe occlusive coronary artery disease and myocardial infarction and die at approximately 6 weeks of age. To determine if this is a general effect of a lack of SR-BI, we generated mice deficient in both SR-BI and the LDL receptor. ::: ::: ::: METHODS AND RESULTS ::: Complete ablation of SR-BI expression in LDL receptor knockout mice resulted in increased plasma cholesterol associated with HDL particles of abnormally large size and a 6-fold increase in diet-induced aortic atherosclerosis but no macroscopic evidence of early-onset coronary artery disease, cardiac pathology, or early death. Furthermore, selective elimination of SR-BI expression in bone marrow-derived cells resulted in increased diet-induced atherosclerosis in LDL receptor knockout mice without concomitant alterations in the distributions of plasma lipoprotein cholesterol. ::: ::: ::: CONCLUSIONS ::: SR-BI expression protects against atherosclerosis in LDL receptor-deficient as well as apolipoprotein E-deficient mice, and its expression in bone marrow-derived cells contributes to this protection. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,762 |
A clinical syndrome combining hypertension and hypokalemic alkalosis led to the diagnosis of primary hyperaldosteronism, caused by a right-sided, 2 cm large, apparently benign aldosterone-producing adenoma. The adrenal tumor was completely resected by laparoscopic adrenalectomy. Six months after surgery, the patient exhibited a severe relapse of hyperaldosteronism. Extensive peritoneal metastases of a mixed aldosterone- and cortisol-secreting adrenocortical carcinoma were found at abdominal laparotomy. In the light of this case report, we discuss the possibility that laparoscopic resection of adrenocortical tumors might contribute to their subsequent peritoneal dissemination. | The whole era of laparoscopic surgery for cancer began with the same optimistic view as for benign disease. However, port-site metastases were published as soon as in 1993. According to literature, it is difficult to estimate exactly the incidence of port-site metastases in laparoscopic colon cancer surgery. Moreover, there are few reports of wound recurrences after open surgery although the incidence is probably about 1%. There are some hypothetical explanations of metastases to the laparoscopic wound, which have not been solved. It can be a haematogenic spread to the wound. Another mechanism could be an aerosol of tumour cells and a third one adhesions of tumour cells to the surface of the instruments or ports. This editorial discusses some of the possible mechanisms of port-site recurrences. Also, most importantly, the justification for laparoscopic surgery for colon cancer is discussed. Only through randomized trials can this question be solved. Therefore, it is mandatory to include patients in a trial and colorectal cancer patients should not undergo laparoscopic surgery outside a clinical randomized trial. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,763 |
Background: Recently, it has been realized that TH1/ TH2 cytokine production offer the unique possibility to predict drug efficacy. However, there is still an incessant need to explore assay conditions and techniques of analyzing cytokines, which are specific and reliable for monitoring drug efficacy. Methods: In this study we used the multiplex bead array technique to detect cytokines of TH1/TH2 cells in whole blood of heart transplanted (HTx) recipients. Results: We found significantly different levels of cytokine expression in HTx recipients compared with cytokine levels in patients prior to HTx. Furthermore, particular cytokine levels were significantly decreased 2 h after drug dosing, compared with cytokine levels before dosing in mitogen-stimulated whole blood. Conclusions: Cytokine analysis with the multiplex array technique in mitogen-stimulated whole blood provides the possibility to predict immunosuppression. q 2006 International Society for Analytical Cytology | Conventional therapeutic drug monitoring based on measuring of blood concentrations (pharmacokinetic) is important in the clinical management of immunosuppressive therapy in transplantation medicine. Since rejection or infection occurs at irregular drug concentrations, immunosuppressive drug therapy is often empiric and prophylactic in nature. In addition, blood immunosuppressant levels are only indirect predictors of the pharmacologic effects on immune cells (pharmacodynamic) because, due to the genetic heterogeneity, the immune systems of the transplant recipients are not equally sensitive to drug effects. Therefore, therapeutic drug monitoring requires the application of reliable and effective methods to study the pharmacodynamic variability by direct measurements of drugs effects on immune cell functions. Against this background we developed assays which are based on whole blood, flow cytometry and biomarkers of diverse functions of T cells and of dendritic cell subsets. These biomarker assays allow us to differentiate between synergistic and antagonistic pharmacodynamic effects of an immunosuppressive drug combination therapy in vitro and to predict the pharmacodynamic drug effects in heart-transplanted recipients. Such a pharmacodynamic drug monitoring based on biomarkers may offer the opportunity to complete conventional therapeutic drug monitoring and, therefore, to tailor immunosuppressive therapy more individually. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,764 |
Sepsis remains a common and serious condition with significant morbidity and mortality due to multiple organ dysfunction, especially acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Sepsis-induced ALI is characterized by injury and dysfunction of the pulmonary microvasculature and pulmonary microvascular endothelial cells (PMVEC), resulting in enhanced pulmonary microvascular sequestration and pulmonary infiltration of polymorphonuclear leukocytes (PMN) as well as disruption of the normal alveolo-capillary permeability barrier with leak of albumin-rich edema fluid into pulmonary interstitium and alveoli. The role of PMVEC death and specifically apoptosis in septic pulmonary microvascular dysfunction in vivo has not been established. In a murine cecal ligation/perforation (CLP) model of sepsis, we quantified and correlated time-dependent changes in pulmonary microvascular Evans blue (EB)-labeled albumin permeability with (1) PMVEC death (propidium iodide [PI]-staining) by both fluorescent intravital videomicroscopy (IVVM) and histology, and (2) PMVEC apoptosis using histologic fluorescent microscopic assessment of a panel of 3 markers: cell surface phosphatidylserine (detected by Annexin V binding), caspase activation (detected by FLIVO labeling), and DNA fragmentation (TUNEL labeling). Compared to sham mice, CLP-sepsis resulted in pulmonary microvascular barrier dysfunction, quantified by increased EB-albumin leak, and PMVEC death (PI+ staining) as early as 2 h and more marked by 4 h after CLP. Septic PMVEC also exhibited increased presence of all 3 markers of apoptosis (Annexin V+, FLIVO+, TUNEL+) as early as 30 mins – 1 h after CLP-sepsis, which all similarly increased markedly until 4 h. The time-dependent changes in septic pulmonary microvascular albumin-permeability barrier dysfunction were highly correlated with PMVEC death (PI+; r = 0.976, p < 0.01) and PMVEC apoptosis (FLIVO+; r = 0.991, p < 0.01). Treatment with the pan-caspase inhibitor Q-VD prior to CLP reduced PMVEC death/apoptosis and attenuated septic pulmonary microvascular dysfunction, including both albumin-permeability barrier dysfunction and pulmonary microvascular PMN sequestration (p < 0.05). Septic PMVEC apoptosis and pulmonary microvascular dysfunction were also abrogated following CLP-sepsis in mice deficient in iNOS (Nos2−/−) or NADPH oxidase (p47phox−/− or gp91phox−/−) and in wild-type mice treated with the NADPH oxidase inhibitor, apocynin. Septic murine pulmonary microvascular dysfunction in vivo is due to PMVEC death, which is mediated through caspase-dependent apoptosis and iNOS/NADPH-oxidase dependent signaling. | BACKGROUND ::: Mesenchymal stem cells (MSC) obviously alleviate the damage of the structure and function of pulmonary vascular endothelial cells (VEC). The therapeutic effects of MSC are significantly different between pulmonary ARDS (ARDSp) and extrapulmonary ARDS (ARDSexp). MicroRNAs (miRNAs), as important media of MSC regulating VEC, are not studied between ARDSp and ARDSexp. We aimed to explore the plasma levels difference of miRNAs that regulate VEC function and are associated with MSC (MSC-VEC-miRNAs) between ARDSp and ARDSexp patients. ::: ::: ::: METHODS ::: MSC-VEC-miRNAs were obtained through reviewing relevant literatures screened in PubMed database. We enrolled 57 ARDS patients within 24 h of admission to the ICU and then collected blood samples, extracted plasma supernatant. Patients' clinical data were collected. Then, plasma expression of MSC-VEC-miRNAs was measured by real-time fluorescence quantitative PCR. Simultaneously, plasma endothelial injury markers VCAM-1, vWF and inflammatory factors TNF-α, IL-10 were detected by ELISA method. ::: ::: ::: RESULTS ::: Fourteen miRNAs were picked out after screening. A total of 57 ARDS patients were included in this study, among which 43 cases pertained to ARDSp group and 14 cases pertained to ARDSexp group. Plasma miR-221 and miR-27b levels in ARDSexp group exhibited significantly lower than that in ARDSp group (miR-221, 0.22 [0.12-0.49] vs. 0.57 [0.22-1.57], P = 0.008, miR-27b, 0.34 [0.10-0.46] vs. 0.60 [0.20-1.46], P = 0.025). Plasma vWF concentration in ARDSexp group exhibited significantly lower than that in ARDSp group (0.77 [0.29-1.54] vs. 1.80 [0.95-3.51], P = 0.048). Significant positive correlation was found between miR-221 and vWF in plasma levels (r = 0.688, P = 0.022). Plasma miR-26a and miR-27a levels in non-survival group exhibited significantly lower than that in survival group (miR-26a, 0.17 [0.08-0.20] vs. 0.69 [0.24-2.33] P = 0.018, miR-27a, 0.23 [0.16-0.58] vs. 1.45 [0.38-3.63], P = 0.021) in ARDSp patients. ::: ::: ::: CONCLUSION ::: Plasma miR-221, miR-27b and vWF levels in ARDSexp group are significantly lower than that in ARDSp group. Plasma miR-26a and miR-27a levels in non-survival group are significantly lower than that in survival group in ARDSp patients. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,765 |
Cirrhotic patients have disturbed systemic hemodynamics with reduced arterial blood pressure, but this has not been investigated during daily activity and sleep. Systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP), and heart rate (HR) were measured by an automatic ambulant device for monitoring blood pressure in 35 patients with cirrhosis and 35 healthy matched controls. During the daytime, SBP, DBP, and MAP were significantly lower in the patients than in the controls (median 118 vs. 127; 70 vs. 78; 86 vs. 94 mm Hg, P < .0001 to P < .05). The nighttime blood pressures were almost similar in the two groups (108 vs. 110; 65 vs. 67; 78 vs. 82 mm Hg, NS). Conversely, HR was significantly higher in the patients both in the daytime (86 vs. 72/min, P < .0001) and at night (80 vs. 64/min, P < .0001). Consequently, the reduction in blood pressure and HR from daytime to nighttime was significantly lower in the patients than in the controls (P < .0001 to P < .01). Multiple regression analysis showed HR, serumalbumin, serum sodium, and clotting factors 2, 7, and 10 as significant independent predictors of SBP in cirrhosis. In conclusion, cirrhotic patients have elevated HR, but surprisingly normal arterial blood pressure during the nighttime, and the circadian variation in blood pressure and HR is diminished, probably because of an almost unaltered cardiac output during the 24 hours. These results may reflect a major defect in the ability of optimal regulation of blood pressure in cirrhotic patients. | Purpose: In patients with massive ascites, large volume paracentesis may be associated with complications as circulatory dysfunction. Selection of appropriate patients might reduce such side effects. Patients and Methods: Forty-fi ve patients known to have liver cirrhosis and presenting with massive ascites were included. There were 27 males and 18 females, with age (mean 51.2+10.64). All patients were subjected to full history, clinical examination, complete blood picture, prothrombin time, serum albumin, total plasma protein, serum bilirubin, serum creatinine, serum electrolytes and plasma renin activity measured by radioimmunoassay. Echocardiographic evaluation for cardiac output, pulmonary artery pressure, diastolic and systolic function before and after paracentesis. Large-volume paracentesis (LVP) ranging 8–18 liters with a mean 9.9 L was performed to all patients. Paracentesis induced circulatory dysfunction (PICD) was defi ned as increase in plasma renin activity (PRA) of more than 50% of pretreatment value to a level greater than 7.5ng /ml/ hour on the 6th day after paracentesis. Results: The incidence of PICD in patients with massive hepatic ascites was 73.3% (87.5% with Dextran and 38.5% with albumin). There were no serious systemic or local side effects one week following LVP. Type of plasma expander and younger ages were the only independent predictors (odd ratio OR with 95% confi dence interval CI, 3.01 Key words: Circulatory dysfunction, hepatic cardiomyopathy, massive hepatic ascites | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,766 |
Doxorubicin is a highly effective cancer treatment whose use is severely limited by dose-dependent cardiotoxicity. It is well established that doxorubicin increases reactive oxygen species (ROS) production. In this study, we investigated contributions to doxorubicin cardiotoxicity from Nox2 NADPH oxidase, an important ROS source in cardiac cells, which is known to modulate several key processes underlying the myocardial response to injury. Nox2-deficient mice (Nox2-/-) and wild-type (WT) controls were injected with doxorubicin (12 mg/kg) or vehicle and studied 8 weeks later. Echocardiography indicated that doxorubicin-induced contractile dysfunction was attenuated in Nox2-/- versus WT mice (fractional shortening: 29.5±1.4 versus 25.7±1.0%; P<0.05). Similarly, in vivo pressure-volume analysis revealed that systolic and diastolic function was preserved in doxorubicin-treated Nox2-/- versus WT mice (ejection fraction: 52.6±2.5 versus 28.5±2.3%, LVdP/dtmin: -8,379±416 versus -5,198±527 mmHg s(-1); end-diastolic pressure-volume relation: 0.051±0.009 versus 0.114±0.012; P<0.001). Furthermore, in response to doxorubicin, Nox2-/- mice exhibited less myocardial atrophy, cardiomyocyte apoptosis, and interstitial fibrosis, together with reduced increases in profibrotic gene expression (procollagen IIIαI, transforming growth factor-β3, and connective tissue growth factor) and matrix metalloproteinase-9 activity, versus WT controls. These alterations were associated with beneficial changes in NADPH oxidase activity, oxidative/nitrosative stress, and inflammatory cell infiltration. We found that adverse effects of doxorubicin were attenuated by acute or chronic treatment with the AT1 receptor antagonist losartan, which is commonly used to reduce blood pressure. Our findings suggest that ROS specifically derived from Nox2 NADPH oxidase make a substantial contribution to several key processes underlying development of cardiac contractile dysfunction and remodeling associated with doxorubicin chemotherapy. | Epidermal growth factor receptor-2 (HER-2) is overexpressed in 20% to 25% of human breast cancers, which is associated with aggressive tumor growth and poor prognosis. Trastuzumab (Herceptin®) is a humanized monoclonal antibody directed against HER-2, the first highly selective form of therapy targeting HER-2 overexpressing tumors. Although initial trials indicated high efficacy and a favorable safety profile of the drug, the first large, randomized trial prompted a retrospective analysis of cardiac dysfunction in prior trials utilizing trastuzumab. There has been ongoing debate on the cardiac safety of trastuzumab since, initiating numerous clinical and preclinical investigations to better understand the background of trastuzumab cardiotoxicity and evaluate its impact on patient morbidity. Hereby, we aim to give a comprehensive overview of our current knowledge on the cardiotoxicity of trastuzumab, primarily focusing on data from clinical trials and highlighting the main molecular mechanisms proposed. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,767 |
In order to compare the effect of dexamethasone and bergenin on chronic bronchitis and to reveal their anti-inflammatory mechanisms, (1)H NMR-based metabolomics was performed to explore the potential biomarkers of the disease and study the therapeutic mechanisms of the drugs. In this study, 40 Sprague-Dawley male rats were randomly divided into 4 groups, namely control, model, dexamethasone and bergenin groups, with 10 rats in each group. Except for the control group, rats from the other three groups were exposed to tobacco smoke for 1 h d(-1) for 28 days. During the modeling, dexamethasone (0.2 mg kg(-1)) and bergenin (87 mg kg(-1)) were administered orally to dexamethasone or bergenin rats 3 h after exposure every day. On the other hand, control and model rats were intragastrically administered water. According to the results of morphometric analysis of the airway epithelium and the count of white blood cells in the bronchoalveolar lavage fluid (BALF), dexamethasone and bergenin could suppress the infiltration of inflammatory cells, inhibit the secretion of mucus, and reduce white blood cells in BALF. Serum samples from the rats' orbits were collected every week. The metabolic profiles of sera were analyzed by multivariate statistical analyses, including PCA, PLS-DA and OPLS-DA models, and 18 metabolites were identified. The dynamic fluctuations of these biomarkers in sera from different groups were detected. The results suggested that the anti-inflammatory mechanism of dexamethasone may be associated with BCAA metabolism and glycolysis while bergenin could change BCAA metabolism, glycine, serine and threonine metabolism, and glycolysis to treat chronic bronchitis. | Chronic obstructive pulmonary disease (COPD), a common and heterogeneous respiratory disease, is characterized by persistent and incompletely reversible airflow limitation. Metabolomics is applied to analyze the difference of metabolic profile based on the low-molecular-weight metabolites (<1 kDa). Emerging metabolomic analysis may provide insights into the pathogenesis and diagnosis of COPD. This review aims to summarize the alteration of metabolites in blood/serum/plasma, urine, exhaled breath condensate, lung tissue samples, etc. from COPD individuals, thereby uncovering the potential pathogenesis of COPD according to the perturbed metabolic pathways. Metabolomic researches have indicated that the dysfunctions of amino acid metabolism, lipid metabolism, energy production pathways, and the imbalance of oxidations and antioxidations might lead to local and systematic inflammation by activating the Nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway and releasing inflammatory cytokines, like interleutin-6 (IL-6), tumor necrosis factor-α, and IL-8. In addition, they might cause protein malnutrition and oxidative stress and contribute to the development and exacerbation of COPD. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,768 |
Galectin-3 and ST2 are emerging biomarkers involved in myocardial fibrosis. We evaluate the relevance of a multiparametric biomarker approach based on increased serum levels of NT-proBNP, galectin-3, and ST2 in stratifying the prognosis of chronic heart failure (CHF) outpatients. In 315 CHF outpatients in stable clinical condition clinical and echocardiographic evaluations were performed. Routine chemistry and serum levels of NT-proBNP, galectin-3, and ST2 were also assessed. During a 12 month follow-up, cardiovascular death, and/or heart failure (HF) occurred in 64 patients. The presence of NT-proBNP, galectin-3, and ST2 were higher than the recommended cutoffs and were all associated with events at univariate Cox regression analysis, as well as in a multivariate analysis including the three biomarkers. When a score based on the number of biomarkers above the recommended cut-offs was used (in a range of 0-3), it was associated with events both with respect to the univariate (HR 2.96, 95% CI 2.21-3.95, p < 0.001, C-index 0.78) and the multivariate (HR 1.52, 95% CI 1.06-2.17, p: 0.023, C-index 0.87) analyses, after correction for the variables of a reference model. Our results suggest that an easy prognostic approach based on the combination of three biomarkers, although with partially-overlapping pathophysiological mechanisms, is able to identify patients with the highest risk of heart failure progression. | Plasma GAL-3 was measured by enzyme-linked immunosorbent assay in patients with HF (n=75), control patients without HF (n=32), and control patients without HF with moderate renal insufficiency (n=12). Compared to controls without HF (14±4 ng/mL), GAL-3 was higher in patients with both acute decompensated HF (23±11 ng/mL) and stable HF (22±10 ng/mL) (P<0.001 versus controls for both) but did not differ between acute decompensated HF and stable HF (P=0.75). Likewise, GAL-3 was elevated in both HF with preserved left ventricular ejection fraction (23±9 ng/mL) and HF with reduced left ventricular ejection fraction (22±11 ng/mL) (P<0.001 versus controls for both) but did not differ between HF with preserved ejection fraction and HF with reduced ejection fraction (P=0.37). GAL-3 correlated strongly with estimated glomerular filtration rate, both in patients with HF (r=0.75, P<0.001) and in patients without HF (r=0.82, P<0.001), and this relationship was unaffected by the presence or absence of clinical HF. Conclusions-—Plasma GAL-3 is inversely related to renal function in patients with and without clinical HF. Concentrations of plasma GAL-3 do not seem to depend on the level of compensation or type of HF. Furthermore, the relationship between GAL-3 and renal function seems to be affected little or not at all by the presence or absence of clinical HF. (J Am Heart Assoc. 2012;1: e000760 doi: 10.1161/JAHA.112.000760) | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,769 |
BACKGROUND ::: Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder which presents with recurrent myoglobinuria. Heterozygotes are usually asymptomatic. ::: ::: ::: METHODS ::: We correlate the clinical, biochemical and molecular features of a family in which the proband is homozygous for CPT II deficiency, due to the common Ser 113 Leu mutation. ::: ::: ::: RESULTS ::: The 20-year-old female proband presented at age three years with episodic myalgia and myoglobinuria, elevated creatine kinase (CK) of 3600 IU/L and had a 33% residual CPT II activity in cultured skin fibroblasts. Her 25-year-old dizygotic twin brothers presented with muscle stiffness following prolonged exercise but no overt pigmenturia and had interictal CKs up to 662 lU/L. Her parents and a 13-year-old brother are asymptomatic. An elder sister, not investigated, had recurrent pigmenturia and died at eight years with myoglobinuria. Molecular analysis revealed that the proband is homozygous for the Ser 113 Leu mutation. Her parents are heterozygotes with CPT II activities of 55% to 70%. Her younger brother is normal with 83% activity. The symptomatic twin brother are heterozygous but demonstrated unexpectedly low CPT II activities of 40%, which may explain their phenotype. ::: ::: ::: CONCLUSION ::: We postulate that there may be genetic, environmental and sex hormonal factors accounting for this manifesting heterozygosity and biochemical heterogeneity in CPT II deficiency. | Carnitine palmitoyltransferase (CPT) II deficiency is one of the most common forms of mitochondrial fatty acid oxidation disorder. Its clinical phenotypes are classified into the muscle, severe infantile, and lethal neonatal forms. Among Caucasians, the muscle form predominates, and the c.338C > T (p.S113L) variant is detected in most cases, whereas among the Japanese, c.1148T > A (p.F383Y) is the variant allele occurring with the highest frequency and can apparently cause symptoms of the severe infantile form. Newborn screening (NBS) for this potentially fatal disease has not been established. We encountered an infantile case of CPT II deficiency not detected in NBS using C16 and C18:1 concentrations as indices, and therefore we adopted the (C16 + C18:1)/C2 ratio as an alternative primary index. As a result, the disease was diagnosed in nine of 31 NBS-positive subjects. The values for (C16 + C18:1)/C2 in the affected newborns partly overlapped with those in unaffected ones. Among several other indices proposed previously, C14/C3 has emerged as a more promising index. Based on these findings, nationwide NBS for CPT II deficiency using both (C16 + C18:1)/C2 and C14/C3 as indices was officially approved and started in April 2018. We diagnosed the disease in four young children presenting with symptoms of the muscle form, whose values for the new indices were not elevated. Although it is still difficult to detect all cases of the muscle form of CPT II deficiency in NBS, our system is expected to save many affected children in Japan with the severe infantile form predominating. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,770 |
Two different ways of administering topical gentamicin were examined in patients undergoing total hip arthroplasty. 160 mg gentamicin, dissolved in isotonic saline, was instilled into the wounds of five out of ten patients. In the other five patients, the components of the prostheses were inserted by means of gentamicin-containing cement, 0.5 g per 40 g powder. Both the serum concentrations and the wound concentrations of gentamicin were determined constantly during the postoperative period. The average half-lives of gentamicin in the surgical wounds of the two groups of patients were found to be 3½ and 25h, respectively. The average wound concentration was found to be higher than the minimum inhibitory concentration for staphylococci and aerobic Gram-negative rods for 18 and 11 h, respectively, in the group of patients treated with gentamicin solution compared with 160 and 67 h, respectively, in the group treated with the gentamicin-containing cement. | f. In the treatment of systemic fungal infections or relevant parasitic infections, we recommend using azole antifungal agents and/or echinocandins rather than conventional amphotericin B or liposomal amphotericin B, if equal therapeutic efficacy can be assumed. (1A) 3. Other methods of prevention of AKI in the critically ill a. We suggest not using N-acetylcysteine (NAC) to prevent AKI in critically ill patients with hypotension. (2D) b. We recommend not using N-acetylcysteine (NAC) to prevent postsurgical AKI. (1A) c. We suggest not using bicarbonate in patients undergoing cardiac surgery with cardiopulmonary bypass with the intent of preventing AKI. (2A) d. We suggest not selecting off pump coronary artery bypass surgery in preference to the same surgery using cardiopulmonary bypass solely for the purpose of reducing peri-operative AKI or the need for RRT. (2C) | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,771 |
OBJECTIVE ::: The aim of this study was to evaluate the feasibility of enteral nutrition (EN) for critically ill trauma patients with severe traumatic duodenal injuries who received placement of concurrent decompressing and feeding jejunostomies. ::: ::: ::: METHODS ::: Adult patients admitted to the trauma intensive care unit from January 2010 to December 2013, given concurrent afferent decompressing and efferent feeding jejunostomies for severe duodenal injury and provided EN or parenteral nutrition (PN), were retrospectively evaluated. Enteral feeding intolerance was defined as an increase in the decompressing jejunostomy drainage volume output, worsening abdominal distension, or cramping/pain unrelated to surgical incisions. Patients who failed initial EN were transitioned to PN. ::: ::: ::: RESULTS ::: Twenty-six patients were enrolled. Of the 24 patients given EN within the first 2 wk posthospitalization, 18 (75%) failed EN within 2 ± 2 d of initiating EN. EN was discontinued when increases were seen in decompressing jejunostomy drainage volume output (n = 11) and output with abdominal pain and/or distension (n = 6), or abdominal pain/distension was seen without an increase in output (n = 1). Jejunostomy drainage volume output increased from 474 ± 425 mL/d to 1168 ± 725 mL/d (P < 0.001) during EN intolerance. More patients with blunt intestinal injury than those with penetrating injuries (75% versus 15%, respectively; P = 0.035) tolerated EN. Patients initially given PN (n = 13) received more calories (P < 0.005) and protein (P < 0.001) than those given initial EN (n = 13). ::: ::: ::: CONCLUSION ::: The majority of patients with severe duodenal injuries and concurrent decompressing/feeding tube jejunostomies failed initial EN therapy. | A method for comparing death rates of groups of injured persons was developed, using hospital and medical examiner data for more than two thousand persons. The first step was determination of the extent to which injury severity as rated by the Abbreviated Injury Scale correlates with patient survival. Substantial correlation was demonstrated. Controlling for severity of the primary injury made it possible to measure the effect on mortality of additional injuries. Injuries that in themselves would not normally be life-threatening were shown to have a marked effect on mortality when they occurred in combination with other injuries. An Injury Severity Score was developed that correlates well with survival and provides a numerical description of the overall severity of injury for patients with multiple trauma. Results of this investigation indicate that the Injury Severity Score represents an important step in solving the problem of summarizing injury severity, especially in patients with multiple trauma. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,772 |
To investigate the role of circulating humoral substances in the pathogenesis of increased vascular wall water and sodium concentration in experimental hypertension, rabbit aortic media explants were cultured in tissue culture medium supplemented (10-20%) with serum obtained from the same dogs (n = 7): 1) before the induction of hypertension; 2) after wrapping one kidney in silk (two-kidney perinephritic hypertension, 2-KPHT); and 3) after contralateral nephrectomy (1-KPHT). Cultures also were run with serum of sham-wrapped and then unilaterally nephrectomized normotensive dogs (n = 4). After 3 weeks of culture, the explants were harvested, and their water, sodium and potassium concentration was measured. Compared to the composition of explants cultured in prehypertensive serum, the water concentration of explants cultured in 1-KPHT and the sodium concentration of explants cultured in 2-KPHT and 1-KPHT serum were increased (p < 0.05). The water and electrolyte content of explants cultured in sera of sham-operated normotensive control dogs was the same regardless of the type of serum used, pre- or post-sham surgery or post-nephrectomy. The effects of serum from hypertensive dogs were not explained by variations in serum creatinine, sodium and potassium levels or in plasma renin activities. The experiments provide evidence for the role of serum factor(s) in the pathogenesis of abnormal vascular wall water and sodium concentration in experimental hypertension. | Segments of pig aortic medial tissue, cultured in a semisynthetic medium, develop a new growth starting about the fourth day. In the first week most cells in this new growth are primitive cells and fibroblast-like cells with only a few modified smooth muscle cells. At this period, only mucopolysaccharides can be identified in the extracellular substances. By the third week, the great majority of cells are modified smooth muscle cells. The extracellular substance is composed of collagen and elastic tissue in addition to mucopolysaccharides. Since the two phenomena, cell proliferation and the production of these specific extracellular substances, are among the most prominent features of early atherosclerosis, it would seem that this in vitro system could be used advantageously in experiments designed to study the role of individual factors implicated in atherogenesis. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,773 |
This report highlights the importance of accurate interpretation of even small intraoperative capnography changes. In this case, an otherwise unexplained sudden small decrease in end-expiratory carbon dioxide tension (P(ET)CO2) led to the detection of a deep venous thrombus. During the surgery of a 34-year-old woman with a known carcinoma of the corpus uteri, who was scheduled for paraaortal lymphadenectomy, a sudden decrease in carbon dioxide tension occurred. In careful exploration of the surgical field to rule out a thromboembolic event, the surgeons noticed an induration of the right iliac vein. A consulting vascular surgeon exposed a right-sided, irregular, double-lumen, common iliac vein with a thrombus the tip of which floated in the inferior vena cava. Following complete thrombectomy, the procedure was accomplished without further adverse events. | OBJECTIVE ::: To explore the correlation and concordance between end-tidal carbon dioxide and arterial carbon dioxide partial pressure, and confirm the experience of the general consensus among service environments. ::: ::: ::: DESIGN ::: A prospective cross-sectional analysis. ::: ::: ::: SETTING ::: Two respiratory service units in Hong Kong. ::: ::: ::: PARTICIPANTS ::: Two hundred respiratory patients were recruited, in whom 219 sets of observations were recorded. Patients deemed to require arterial blood gas determination also had their end-tidal carbon dioxide partial pressure measured at that time, using two LifeSense LS1-9R Capnometers. ::: ::: ::: MAIN OUTCOME MEASURES ::: The agreement of end-tidal carbon dioxide partial pressure and arterial carbon dioxide partial pressure was studied by correlation coefficients, mean and standard deviation of their difference, and the Bland-Altman plot. ::: ::: ::: RESULTS ::: Overall, the correlation was low and insignificant (r=0.1185, P=0.0801). The mean of the difference was 7.2 torr (95% confidence interval, 5.5-8.9) and significant (P<0.001). The limits of agreement by Bland-Altman analysis were -18.1 to 32.5 torr, which were too large to be acceptable. In the sub-group on room air, the mean difference was reduced to 2.26 torr, the correlation between end-tidal carbon dioxide partial pressure and arterial carbon dioxide partial pressure was 0.2194 (P=0.0068), though statistically significant, the extent of correlation was still low. ::: ::: ::: CONCLUSION ::: End-tidal carbon dioxide partial pressure did not show significant correlation or concordance with arterial carbon dioxide partial pressure, especially when supplemental oxygen was used. End-tidal carbon dioxide partial pressure currently cannot replace arterial blood gas measurement as a tool for monitoring arterial carbon dioxide partial pressure. Possible reasons for the discrepancy with previous studies include small sample size in previous studies, lack of research facilities in service settings, and publication bias against negative studies. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,774 |
BACKGROUND: Oral lichen planus (OLP) and graft-vs.-host disease (GVHD) are conditions with increased risk of malignant transformation to squamous cell carcinoma of the head and neck (SCCHN). The p6 ... | The corneal surface is an essential organ necessary for vision, and its clarity must be maintained. The corneal epithelium is renewed by limbal stem cells, located in the limbus and in palisades of Vogt. Palisades of Vogt maintain the clearness of the corneal epithelium by blocking the growth of conjunctival epithelium and the invasion of blood vessels over the cornea. The limbal region can be damaged by chemical burns, physical damage (e.g., by contact lenses), congenital disease, chronic inflammation, or limbal surgeries. The degree of limbus damage is associated with the degree of limbal stem cells deficiency (partial or total). For a long time, the only treatment to restore vision was grafting part of the healthy cornea from the other eye of the patient or by transplanting a cornea from cadavers. The regenerative medicine and stem cell therapies have been applied to restore normal vision using different methodologies. The source of stem cells varies from embryonic stem cells, mesenchymal stem cells, to induced pluripotent stem cells. This review focuses on the use of oral mucosa epithelial stem cells and their use in engineering cell sheets to treat limbal stem cell deficient patients. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,775 |
In the epidermis, tight junction (TJ) structure is specifically located in the stratum granulosum, where the expression of ΔNp63, a p53 family transcription factor, is attenuated. Since the relationship between ΔNp63 and barrier function has not been fully uncovered, we assessed expression profiles of TJ proteins in skin tissues and cultured keratinocytes. The results showed that expression of ΔNp63 and that of claudin-4 were inversely correlated in healthy human epidermis. In vitro studies using HaCaT keratinocytes revealed functional relevance of ΔNp63 and claudin-4. Curiously, Toll-like receptor (TLR)-3 ligand, which is known to be liberated from damaged cells, suppressed ΔNp63 expression and concomitantly upregulated claudin-4 expression in primary keratinocytes. More interestingly, a broad expression pattern of claudin-4 was found in the epidermis of atopic dermatitis (AD), a barrier defect disorder, which contains ΔNp63-lacking keratinocytes as we reported previously. Therefore, upregulation of claudin-4 expression regulated by ΔNp63 might be associated with complementary or repair responses of damaged keratinocytes with AD. | All-trans retinoic acid (ATRA) regulates skin cell proliferation and differentiation. ATRA is widely used in the treatment of skin diseases, but results in irritation, dryness and peeling, possibly due to an impaired skin barrier, although the exact mechanisms are unclear. The present study established an ATRA-associated dermatitis mouse model (n=32) in order to examine the molecular mechanisms of skin barrier impairment by ATRA. Changes in epidermal morphology and structure were observed using histological examination and transmission electron microscopy (TEM). Gene expression was analyzed by microarray chip assay. Histology and TEM demonstrated pronounced epidermal hyperproliferation and parakeratosis upon ATRA application. The stratum corneum layer displayed abnormal lipid droplets and cell-cell junctions, suggesting alterations in lipid metabolism and dysfunctional cell junctions. Gene expression profiling revealed that factors associated with epidermal barrier function were differentially expressed by ATRA, including those associated with tight junctions (TJs), cornified envelopes, lipids, proteases, protease inhibitors and transcription factors. In the mouse epidermis, Claudin-1 and -4 are proteins involved in TJs and have key roles in epidermal barrier function. ATRA reduced the expression and altered the localization of Claudin-1 in HaCaT immortalized keratinocytes and the mouse epidermis, which likely leads to the disruption of the epidermal barrier. By contrast, Claudin-4 was upregulated in HaCaT cells and the mouse epidermis following treatment with ATRA. In conclusion, ATRA exerts a dual effect on epidermal barrier genes: It downregulates the expression of Claudin-1 and upregulates the expression of Claudin-4. Claudin-4 upregulation may be a compensatory response for the disrupted barrier function caused by Claudin-1 downregulation. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,776 |
Snake bite is the common cause of morbidity and mortality in India. Snake antivenom, although very effective, is expensive, scarce, and associated with side effects. The conventional dose may not be required in all cases and a smaller dose may be as effective. A randomized double blind controlled trial was conducted to compare the effect of lower versus the conventional (high) dose. Patients presenting within 24 hours of snake bite with hematological or neurological evidence of systemic envenomation were included in the study. Patients were randomized either to receive high dose (2 vials over 1 hour, followed by 2 vials over 4 hours and repeated 4 hourly until clotting parameters normalized and then 2 vials as infusion over 24 hours) or low dose (2 vials over 1 hour, followed by 1 vial over four hours, repeated 4 hourly until clotting parameters were normalized and then 1 vial as an infusion over 24 hours). Thirty one patients received high dose and 29 a low dose. The mean dose of antivenom used was significantly different in the two groups (8.9 and 4.7, respectively). There was no mortality. The duration of stay was 4.94 and 3.48 days, respectively. There was no difference in the transfusion, dialysis or ventilation requirement of the two groups. Low dose regimen is more effective and required 5 vials less than the conventional dose. Each vial costs Rs. 200, so the estimated savings is Rs. 1000 per patient. | Snake bite incidence is highest in Asia and sub-Saharan Africa. This retrospective audit of 533 adult patients, who had presented to the Emergency Department, collates clinical features, effect of pharmacologic interventions and the risk factors that influence morbidity and mortality. Dual toxicity, neurological and haematological, was observed in 30.4% of patients. Laboratory evidence of haematotoxicity was demonstrated in 314 (58.9%) and 40% demonstrated clinical evidence of bleeding. However, 7.3% of these patients did not have laboratory evidence of bleeding disorder (p < 0.001). Conversely, 60% did not have clinical evidence of bleeding, but demonstrated laboratory evidence of abnormal parameters. Acute kidney injury (AKI) was evident in 28% of patients and 15.3% required haemodialysis. About 25% with no haematotoxicity showed evidence of AKI. The majority received 6–12 vials of poly-valent anti-snake venom. Hypersensitivity reaction rate was 8% and predominantly anaphylactoid in nature. The length of hospital stay ranged from 2 to 28 days and 20% required mechanical ventilation. Overall mortality rate was 7.5% with significant association to AKI, haematotoxicity and assisted ventilation. The mortality rate was 18% in patients with pre-hospital delay more than 24 h, as against 5% when admitted within the above specified period (p = <0.001). The strength of this study is the accrued information of over a period of 10 years of snake-bite management through the Emergency Department of a university hospital setting. The limitations are the retrospective study design and the rejection percentage of 15.5% due to insufficient information from the total chart pool. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,777 |
Aims Clinical complaints on the first-line of cardiovascular medications make continuous search for new drugs a necessity. This study evaluated the cardiovascular effects and mechanism of 4-[(1-phenyl-1 H -pyrazol-4-yl)methyl]1-piperazine carboxylic acid ethyl ester (LQFM008). Main methods Normotensive male Wistar or spontaneously hypertensive rats (anesthetized or conscious) were used to evaluate the effect of LQFM008 on the mean arterial pressure (MAP), heart rate (HR), arterial blood flow (ABF), arterial vascular conductance (AVC), baroreflex effectiveness index (BI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and vascular function. Key findings In anesthetized normotensive rats, LQFM008 (7.3, 14.3 or 28.6 μmol/kg, iv) reduced MAP (− 21.1 ± 2.7; − 23.9 ± 4.7 or − 32.4 ± 8.3 mm Hg, respectively) and AVC (22%, 32% or 38%) in a dose-dependent manner. LQFM008 elicited a temporal reduction in the SBP and DBP without changes to the BI of conscious normotensive rats. In hypertensive rats, LQFM008 (7.3, 14.3 or 28.6 μmol/kg, iv) reduced MAP ( −2.3 ± 2.6; − 29.3 ± 2.7 or −38.4 ± 2.8 mmHg, respectively) and increased HR (1.6 ± 3.7; 15.4 ± 4.9 or 25.5 ± 6.2 bmp, respectively) in a dose-dependent manner. A week of oral administration of LQFM008 47.7 μmol/kg elicited a temporal reduction in SBP of hypertensive rats. Pretreatments with atropine, WAY-100635 or L-NAME blocked the effect of LQFM008. In addition, LQFM008-induced endothelium-dependent vascular relaxation was inhibited by L-NAME. Significance Our findings showed hypotensive, antihypertensive and vasorelaxant effects of LQFM008 and suggest the participation of nitric oxide, 5-HT1A and muscarinic receptors. | This paper is a review on the types of antagonists and the signaling mechanism pathways that have been used to determine the mechanisms of action employed for vasodilation by test compounds. Thus, we exhaustively reviewed and analyzed reports related to this topic published in PubMed between the years of 2010 till 2015. The aim of this paperis to suggest the most appropriate type of antagonists that correspond to receptors that would be involved during the mechanistic studies, as well as the latest signaling pathways trends that are being studied in order to determine the route(s) that atest compound employs for inducing vasodilation. The methods to perform the mechanism studies were included. Fundamentally, the affinity, specificity and selectivity of the antagonists to their receptors or enzymes were clearly elaborated as well as the solubility and reversibility. All the signaling pathways on the mechanisms of action involved in the vascular tone regulation have been well described in previous review articles. However, the most appropriate antagonists that should be utilized have never been suggested and elaborated before, hence the reason for this review. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,778 |
Objectives: To analyse the periodontal inflammatory infiltrates in patients with cardiac disease, some of these patients were treated with calcium antagonists (nifedipine and diltiazem) and some were not, to compare them with a healthy control group, and to evaluate the changes in the inflammatory infiltrate after periodontal treatment. ::: ::: Material and methods: A “healthy group” (HG, n=12), a “cardiac group” (CG, n=12) without treatment with calcium antagonists, a “nifedipine group” (NG, n=18) and a “diltiazem group” (DG, n=13) were analysed. Biopsies were taken from a zone 2–3 mm below the upper part of the interproximal papillae 12–13 and 33–32 before causal periodontal treatment and after 1 year. Using haematoxylin-eosin staining, the plasma cells (P), lymphocytes (L), histiocytes (H) and polymorphonuclear cells (PMN) were counted. T and B lymphocytes were evaluated using the monoclonal antibodies anti-CD20 and anti-CD45RO. Statistical tests used: χ2 for study of the sample composition; ANOVA for comparison between groups; Student t-test and Wilcoxon test for comparison between visits; post-hoc test Bonferroni. ::: ::: Results: When the cells were compared statistically, differences were stablished for L at the first visit (p<0.00001) and at the last visit (p<0.02), for the B lymphocytes (first visit p<0.0021, last visit p<0.022) and for the T lymphocytes (first visit p<0.0042, last visit p<0.0021). Between the 2 visits, HG showed significant reductions for P (p<0.01), L (p<0.045) and H (p<0.033); and the NG for L (p<0.0001). Lymphocytes showed differences in the NG with respect to the B lymphocytes (p<0.008). ::: ::: Conclusions: Nifedipine affects the inflammatory infiltrate with a greater number of lymphocytes (especially B) and these cells fell significantly in number after periodontal treatment. | Verapamil is an effective prophylactic treatment for cluster headaches and, therefore, is widely used. This report describes four patients with cluster headache who developed gingival enlargement after initiating treatment with verapamil. In two patients, it was possible to control this side effect adequately by optimising oral hygiene and dental plaque control. In the other two patients, lowering of the verapamil dose, in addition to optimal oral hygiene and dental plaque control, was necessary; in one patient verapamil had to be stopped completely to reverse the gingival enlargement. Doctors treating cluster headache with verapamil need to be aware of this side effect, especially as it may be preventable with good dental hygiene and dental plaque control, is reversible with reduction or cessation of verapamil, and can lead to dental loss. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,779 |
The aim of the study was to compare the safety and effectiveness of as-needed formoterol with salbutamol in a large international real-life asthma study. Children and adults (n=18,124) were randomised to 6 months as-needed treatment with open-label formoterol 4.5 microg Turbuhaler or salbutamol 200 microg pressurised metered dose inhaler or equivalent. Primary safety variables were asthma-related and nonasthma-related serious adverse events (SAE)s and adverse events (AE)s resulting in discontinuation (DAE)s. The primary efficacy variable was time to first asthma exacerbation. The incidences of AEs, SAEs and DAEs arising from SAEs were not significantly different between treatments. DAEs for nonserious AEs were higher with formoterol. Asthma-related AEs decreased with formoterol (1,098 (12.3%) versus 1,206 (13.5%)), asthma-related SAEs were similar (108 (1.2%) versus 121 (1.4%)) but more asthma-related DAEs occurred in the formoterol group (89 (1.0%) versus 48 (0.5%)). Time to first exacerbation was prolonged (hazard ratio 0.86) and less as-needed and maintenance medication was used with formoterol. Reductions of exacerbations with as-needed formoterol versus salbutamol increased with increasing age and asthma medication level. This real-life study demonstrates that formoterol as-needed has a similar safety profile to salbutamol, and its use as a reliever therapy is associated with fewer asthma symptoms and exacerbations. | OBJECTIVE ::: To perform a critical comparison between the Brazilian national essential medicines list (Rename, 2012) with the list of essential medicines for children (LEMC, 2011) of the World Health Organization (WHO), regarding the differences among drugs and formulations listed for children. ::: ::: ::: METHODS ::: The LEMC drugs were classified into four categories: 1) absent in Rename; 2) included in Rename but without any formulation suitable for children; 3) listed in Rename only in some formulations; 4) present in Rename in all formulations. The missing formulations were analyzed by therapeutic group. Alternatives present in Rename were searched. ::: ::: ::: RESULTS ::: From the 261 drugs of interest on the LEMC, 30.3% are absent from Rename, 11.1% are in Rename but without any pediatric formulation, and 32.2% are present in some but not all formulations listed in LEMC. Considering all formulations items listed in the LEMC (n = 577), 349 are missing from Rename, of these 19.6% due to their strength, and 18.5% due to the the dosage form. Useful formulations specific for neonatal care, respiratory tract, central nervous system, and anti-infectives, among other groups, are missing. ::: ::: ::: CONCLUSION ::: The lack of age-appropriate formulations of essential medicines for children in Brazil includes important therapeutic groups and indispensable drugs for severe clinical conditions. Some of these products exist in the Brazilian pharmaceutical market, but not in public facilities; others could be produced by national laboratories with commercial interest or stimulated by a specific governmental policy, as in other countries. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,780 |
Previous in vitro studies on human tendon cells (tenocytes) have demonstrated that the exogenous administration of substance P (SP) and acetylcholine (ACh) independently result in tenocyte proliferation, which is a prominent feature of tendinosis. Interestingly, the possible link between SP and ACh has not yet been explored in human tenocytes. Recent studies in other cell types demonstrate that both SP and ACh independently upregulate TGF-β1 expression via their respective receptors, the neurokinin 1 receptor (NK-1R) and muscarinic ACh receptors (mAChRs). Furthermore, TGF-β1 has been shown to downregulate NK-1R expression in human keratocytes. The aim of this study was to examine if TGF-β1 is the intermediary player involved in mediating the proliferative pathway shared by SP and ACh in human tenocytes. The results showed that exogenous administration of SP and ACh both caused significant upregulation of TGF-β1 at the mRNA and protein levels. Exposing cells to TGF-β1 resulted in increased cell viability of tenocytes, which was blocked in the presence of the TGFβRI/II kinase inhibitor. In addition, the proliferative effects of SP and ACh on tenocytes were reduced by the TGFβRI/II kinase inhibitor; this supports the hypothesis that the proliferative effects of these signal substances are mediated via the TGF-β axis. Furthermore, exogenous TGF-β1 downregulated NK-1R and mAChRs expression at both the mRNA and protein levels, and these effects were negated by simultaneous exposure to the TGFβRI/II kinase inhibitor, suggesting a negative feedback loop. In conclusion, the results indicate that TGF-β1 is the intermediary player through which the proliferative actions of both SP and ACh converge mechanistically. | Tumor necrosis factor-α (TNF-α) has been shown to have a catabolic effect on intervertebral disc degeneration (IVDD), including increasing MMP3 expression and subsequent extracellular matrix (ECM) degradation. In contrast, transforming growth factor-β1 (TGF-β1) has an anabolic effect on nucleus pulposus (NP) cells. However, the anti-catabolic effect of TGF-β1 under inflammatory condition is unknown. The aim of this study was to demonstrate whether TGF-β1 can reverse TNF-α-induced MMP3 increase in NP cells and to further investigate the underlying mechanisms. The transcriptional activity, gene expression, and protein levels of MMP3 were measured by luciferase reporter assay, qRT-PCR and western blot, respectively. TNF-α increased MMP3 expression in rat NP cells time and dose dependently. TGF-β1 could abolish TNF-α-mediated up-regulation of collagen I and MMP3 expression, and down-regulate aggrecan and collagen II expression. The ERK1/2 signaling pathway was activated after exposure to TGF-β1. Treatment with ERK1/2 inhibitors (PD98059 and U0126) abolished the antagonistic effect of TGF-β1 on TNF-α mediated catabolic responses. These findings provide novel evidence supporting the anti-catabolic role of TGF-β1 in IVDD, which is important for the potential clinical application of TGF-β1 in disc degenerative disorders. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,781 |
Loading and unloading experiments using intestinal sacs and renal cortex slices were undertaken to ascertain the role of amino acid efflux in cycloleucine-induced amino-aciduria. The presence of cycloleucine, lysine, or valine on the luminal or antiluminal side of the intestine caused an increased leakage of [ 14 C] cycloleucine, [ 14 C] lysine, and [ 35 S] cystine from the tissue. Similar results were obtained when using kidney cortex slices, except for cystine efflux. The latter phenomenon was inhibited by cycloleucine and lysine. Data, also obtained with renal cortex slices, suggest that cystine and cysteine are recognized by different transport sites although one (the oxidized form) may be typically extracellular and the other (the reduced form), intracellular. A comparison of these data with previous works done in our laboratory 14 shows that cycloleucine affects efflux less than influx and further suggests that in rats given cycloleucine, renal transport is impaired only at the brush border level for cystine and at both luminal and antiluminal membranes for dibasic amino acids. | In microperfusion experiments renal tubular reabsorption of 35S- and 14C-labelled L-cysteine (= cys), L-cystine (= cys-cys), and L-cystathionine was measured in vivo et situ at different initial concentrations. The interactions of cys and cys-cys with several neutral amino acids were investigated. The cys reabsorption mechanism was found to be saturable and has a high capacity and a low affinity for cys. An Jmax-value of 3.22 +/- 0.88 nmol X m-1 X s-1 and a Km-value of 7.5 +/- 0.7 mmol X l-1 were estimated. A saturation of cys-cys reabsorption could not be demonstrated. The fractional reabsorption rate (= FRR) of cys-cys was about 85% at initial concentrations of 0.01, 0.08, and 0.4 mmol X l-1 after a perfusion distance of 2 mm. The FRR of L-cystathionine at an initial concentration of 0.115 mmol X l-1 was only 30% under the same conditions. After perfusion of tubule segments between late proximal and early distal loops the recovery of cys, cys-cys, and cystathionine was smaller than 10%. The FRR of cys was decreased only by L-methionine. Six other neutral amino acids had no effect. On the other hand the FRR of cys-cys was reduced significantly by any of the tested neutral amino acids. The inhibitory effect increased in the order L-alanine less than L-methionine less than L-citrulline less than alpha-aminoisobutyric acid less than L-phenylalanine less than cycloleucine. The FRR of L-methionine and L-phenylalanine was slightly reduced in the presence of cys. It is concluded from these results that cys-cys shares a transport system with other neutral amino acids which is not identical with the reabsorption mechanism for cys. Reabsorption of cys, cys-cy, and cystathionine occurs also in a tubular section between late proximal and early distal sites. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,782 |
OBJECTIVE ::: The objective of this study was to evaluate if the anti-inflammatory properties of bisphosphonates and their effect on bone turnover could be useful in the treatment of AS. ::: ::: ::: METHODS ::: Sixty patients were consecutively assigned in a 1:1 ratio in a 6-month open-label, single-centre study on active AS to receive monthly i.v. neridronate (100 mg) or standard infliximab (5 mg/kg) therapy. ::: ::: ::: RESULTS ::: A significant reduction in the mean BASDAI was observed over 6 months of either neridronate (-1.72) or infliximab (-1.62) administration. The BASFI decreased significantly at 3 and 6 months in the neridronate arm, while in the infliximab group a significant reduction at 3 months but not 6 months was observed. The 10-cm visual analogue scale for axial pain decreased significantly and comparably at 3 and 6 months in both groups. No significant differences between treatment arms for all these changes were observed at both 3 months and the final assessment. The BASMI was not significantly modified in the neridronate or infliximab group. No significant variations of BMD were observed in the infliximab group, while in patients treated with neridronate a significant increase was observed at the lumbar spine. ::: ::: ::: CONCLUSION ::: High i.v. doses of the amino-bisphosphonate neridronate are as effective as infliximab therapy in reducing disease activity in AS patients, with additional benefits on BMD changes. Further studies to confirm these results over a longer time frame are warranted together with the possibility to explore the long-term efficacy of a combination of lower anti-TNF doses with bisphosphonates. | The aim of this study was to explore whether desensitization to the occurrence of the acute-phase response (APR) in patients previously treated with amino-bisphosphonates (N-BPs) is due to a long-lasting reduction in the number of circulating γδ T cells. Circulating lymphocyte subpopulation counts were obtained from 63 patients with postmenopausal or senile osteoporosis at baseline and after 2 days and 12 months of the first intravenous (IV) 5 mg zoledronic acid (ZOL) infusion. At baseline both the proportion and absolute number of circulating γδ T cells were significantly higher in patients who had never used N-BPs vs. previous users, either oral or IV. A typical APR was observed in none of the patients given IV ZOL a year earlier, in 6 (22 %) of the patients previously treated with oral N-BPs, and in 13 (57 %) of the patients naive to any N-BP treatment. In patients naive to N-BPs, a significant reduction in both total lymphocytes and their subsets was observed 2 days after ZOL infusion; all these changes returned to baseline values 1 year later with the exception of γδ T cells, which remained significantly lower in terms of both proportion and absolute number. These results indicate for the first time that both IV and oral N-BP treatments are associated with a long-lasting decrease in circulating γδ T cells, and this may explain the lower incidence of APR in patients previously exposed to N-BPs. Other clinical implications of this sustained effect of N-BPs on immune-regulatory cells might be important. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,783 |
Selenium and coenzyme Q10 (SeQ10) are important for normal cellular function. Low selenium intake leads to increased cardiovascular mortality. Intervention with these substances with healthy elderly persons over a period of four years in a double-blind, randomised placebo-controlled prospective study showed reduced cardiovascular mortality, increased cardiac function, and a lower level of NT-proBNP. Therefore, we wanted to evaluate changes in biochemical pathways as a result of the intervention with SeQ10 using metabolic profiling. From a population of 443 healthy elderly individuals that were given 200 µg selenium and 200 mg coenzyme Q10, or placebo daily for four years, we selected nine males on active intervention and nine males on placebo for metabolic profiling in the main study. To confirm the results, two validation studies (study 1 n = 60 males, study 2 n = 37 males) were conducted. Principal component analyses were used on clinical and demographic data to select representative sets of samples for analysis and to divide the samples into batches for analysis. Gas chromatography time-of-flight mass spectrometry-based metabolomics was applied. The metabolite data were evaluated using univariate and multivariate approaches, mainly T-tests and orthogonal projections to latent structures (OPLS) analyses. Out of 95 identified metabolites, 19 were significantly decreased due to the intervention after 18 months of intervention. Significant changes could be seen in the pentose phosphate, the mevalonate, the beta-oxidation and the xanthine oxidase pathways. The intervention also resulted in changes in the urea cycle, and increases in the levels of the precursors to neurotransmitters of the brain. This adds information to previous published results reporting decreased oxidative stress and inflammation. This is the first-time metabolic profiling has been applied to elucidate the mechanisms behind an intervention with SeQ10. The study is small and should be regarded as hypothesis-generating; however, the results are interesting and, therefore, further research in the area is needed. This study was registered at Clinicaltrials.gov, with the identifier NCT01443780. | Decreased antioxidant capacity and increased oxidative stress have been observed in fibromyalgia patients. Some trials have also shown that CoQ10 levels are reduced in these patients but that supplementation can restore levels and reduce fibromyalgia symptoms, including pain and fatigue. We evaluated the effect of administration of a finished form of CoQ10 (DDM Chinone®) at a dose of 200 mg×2/day in 22 female subjects with a diagnosis of fibromyalgia in a randomized, open-label, cross-over study. Our results show that, compared to a control group, administration of CoQ10 significantly improved most pain-related outcomes by 24-37%, including fatigue (by ~22%) and sleep disturbance (by ~33%). These results confirm the considerable role played by CoQ10 in reducing pain, fatigue, and sleep disturbance in subjects affected by fibromyalgia. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,784 |
Objectives To assess the role of aquaporins (AQPs) in the regulation of amniotic fluid (AF) volume, we determined AF volume and composition and placental and fetal membrane AQP expression throughout the second half of murine gestation. Methods Pregnant CD1 mice were sacrificed at e10–19 and AF volume and composition determined. Placenta and fetal membranes were screened for AQP gene expression. AQP gene expression was quantified by real-time RT PCR and protein location determined by immunohistochemistry. Changes in AF volume were correlated with AQP expression. Results Both membranes and placenta demonstrated expression of AQP1, -3, -8 and -9. Advancing gestation was associated with increased AF volume from e10 to e16, with a marked decrease in AF volume from e16 to e19. By immunohistochemistry, AQP1 was localized to placental vessels and AQP3 to trophoblast. AF volume was negatively correlated with fetal membrane AQP1 and placental AQP1 and AQP9 expression, and positively correlated with placental AQP3 expression. Conclusion Changes in AQPs with advancing gestation, and their correlation with AF volume, suggest a role in mediating placental and membrane water flow and ultimately AF volume. AQP1 appears to regulate fetal membrane water flow, and AQP3 is a likely candidate for the regulation of placental water flow. | CONTEXT ::: During pregnancy, aquaporins (AQPs) expressed in fetal membranes are essential for controlling the homeostasis of the amniotic volume, but their regulation by insulin was never explored in diabetic women. ::: ::: ::: OBJECTIVE ::: The aim of our study was to investigate the involvement of AQPs 1, 3, 8, and 9 expressed in fetal membranes in diabetic parturient women and the control of their expression by insulin. ::: ::: ::: DESIGN AND PARTICIPANTS ::: From 129 fetal membranes in four populations (controls, type 1, type 2 [T2D], and gestational diabetes [GD]), we established an expression AQP profile. In a second step, the amnion was used to study the control of the expression and functions of AQPs 3 and 9 by insulin. ::: ::: ::: MAIN OUTCOMES AND MEASURES ::: The expression of transcripts and proteins of AQPs was studied by quantitative RT-PCR and ELISA. We analyzed the regulation by insulin of the expression of AQPs 3 and 9 in the amnion. A tritiated glycerol test enabled us to measure the impact of insulin on the functional characteristics. Using an inhibitor of phosphatidylinositol 3-kinase, we analyzed the insulin intracellular signaling pathway. ::: ::: ::: RESULTS ::: The expression of AQP3 protein was significantly weaker in groups T2D and GD. In nondiabetic fetal membranes, we showed for the amnion (but not for the chorion) a significant repression by insulin of the transcriptional expression of AQPs 3 and 9, which was blocked by a phosphatidylinositol 3-kinase inhibitor. ::: ::: ::: CONCLUSION ::: In fetal membranes, the repression of AQP3 protein expression and functions observed in vivo is allowed by the hyperinsulinism described in pregnant women with T2D or GD. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,785 |
OBJECTIVE: To examine the risk of aspiration for liquid versus paste bolus consistencies in patients with unilateral vocal cord paralysis (UVCP). METHODS: The swallowing function of adult patients with UVCP was prospectively studied videofluoro-graphically to examine the incidence of laryngeal penetration and aspiration for both liquid and paste boluses. The degree of penetration or aspiration was quantified using the penetration-aspiration scale (PAS). The presence and location of pharyngeal bolus residue were also documented for each consistency. Results were compared between liquid and paste bolus consistencies. RESULTS: Fifty-five patients with UVCP were studied with a mean age of 60.2 years. Intrathoracic surgery or malignancy accounted for 38 (69.1%) of cases. The mean PAS scores for liquid and paste bolus consistency were 3.1 vs. 1.5, respectively (P < 0.001). The liquid bolus penetrated in 19 (34.5%) patients and was aspirated in 11 (20%) patients. In contrast, the paste bolus penetrated in 12 (21.8%) cases and was aspirated in 0 cases (P < 0.001). Pharyngeal residue was more likely to occur at the base of the tongue or vallecula for the paste bolus consistency versus the liquid bolus. CONCLUSIONS: A significant percentage of patients with UVCP will aspirate thin liquids. Paste bolus consistencies are safer for patients with UVCP as they are much less likely to lead to penetration or aspiration despite a higher prevalence of pharyngeal residue. | The penetration-aspiration scale (PAS) is an 8-point scale used to characterize the depth and response to airway invasion during videofluoroscopy. Though widely used in the field of deglutition, there is a lack of consensus regarding the statistical properties of the scale. In order to better understand the state of the literature and the statistical use of the PAS, a systematic review was undertaken to descriptively examine trends in statistical and reporting practices of the PAS since its inception. Online databases were searched for studies citing the original PAS article, which yielded 754 unique articles. Of these, 183 studies were included in the review. Results showed inconsistencies in the statistical use of the scale; 79 studies treated the PAS as ordinal, 71 as categorical, and 49 as interval. Ten types of categorizations were identified. Reporting of power analyses (9%), as well as inter- (26%) and intra-rater (17%) reliability, was uncommon. Among studies that administered multiple bolus volumes or consistencies, 55% reported PAS analyses at the participant/group level only. This review confirms the existence of discrepancies in the statistical treatment of the PAS. A lack of consensus among researchers limits comparisons between studies. The approach to handling this scale dictates the statistical tests used, potentially affecting results and interpretations. Consistent application of statistically sound approaches to PAS analyses is vital for the future of deglutition research. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,786 |
We studied the effects of site of injection on the serum concentration of lidocaine following total spinal block. Six mg.kg-1 of lidocaine was given into the cervical (n = 11) or lumbar (n = 7) subarachnoid space in 10 patients. The mean maximum serum concentration of lidocaine in the cervical group was found to be significantly greater than that in the lumbar group. Lidocaine given into the cervical subarachnoid space seems to be infiltrated easily into the intracranial space and consequently into the systemic circulation. | Stereotactic biopsy is presently performed routinely in the histological diagnosis of brain tumors before the start of chemotherapy. We present a case of accidental total subarachnoid block (TSB) [1] in which neurosurgical stereotactic operations were repeatedly conducted under local anesthesia. There are reports of accidental TSB following durapuncture in spinal epidural anesthesia or intentional TSB for the treatment of intractable pain [2]. Our report describes a case of unexpected, temporary coma and apnea that are presumed to have resulted from accidental direct penetration of a local anesthetic agent into the cerebral ventricular system during local scalp anesthesia. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,787 |
We studied clinical and histologic parameters at the time of renal biopsy of 19 patients with idiopathic membranous nephropathy (IMN) to investigate the predictors for prognosis of IMN. Nineteen patients diagnosed by open renal biopsy between 1988 and 1993 and followed for at least 5 years were divided into two groups according to the latest follow-up renal function. Group I included 16 patients with normal renal function at the last follow-up point. Group II included three patients with end-stage renal failure at the last follow-up point. Antibodies to CD68, CD45RO, alpha-SMA, collagen IV, and collagen VI were used to investigate glomerular and interstitial changes in biopsy specimens by the indirect enzyme-labeled antibody method. Degree of global glomerulosclerosis, segmental glomerulosclerosis, adhesion to Bowman's capsule, and crescent formation were evaluated by light microscopy (periodic acid-Schiff, periodic acid-metheramine [PAM] staining). The difference between the two groups was analyzed by Mann-Whitney U: test. The number of interstitial cells, the number of interstitial CD45RO-positive cells, and increases of interstitial collagen IV and VI were found to be the most important factors for prognosis of IMN. These findings suggest that the extent of tubulointerstitial changes (cellular infiltration and fibrosis) determines the prognosis of renal function in IMN. | The concurrent antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) and membranous nephropathy (MN) have been increasingly documented, mainly in case studies and case series; however, the differences of clinical and pathologic characteristics as well as outcomes between ANCA-GN patients with and without MN remain unclear. The current study investigated the clinical and immunologic features of patients with combined ANCA-GN and MN in a large cohort. Twenty-seven of 223 patients had combined ANCA-GN and MN; they had significantly higher levels of initial serum creatinine, higher Birmingham Vasculitis Activity Score and poorer renal outcome than ANCA-GN patients without MN (P < 0.05). ANCA-GN patients with MN could recognize the light chain of myeloperoxidase more frequently than those without MN (P < 0.05). The prevalence of circulating anti-PLA2R antibodies and glomerular PLA2R deposits was significantly lower in patients with combined ANCA-GN and MN than that in patients with idiopathic MN (P < 0.05). Compared with the idiopathic MN patients, the patients with combined ANCA-GN and MN had significantly higher recognition frequency of immunoglobulin (Ig) G2 and IgG3, and significantly lower recognition frequency of IgG4 (P < 0.05). Patients with combined ANCA-GN and MN had distinct clinical features and a different pathogenesis of MN. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,788 |
Pain is a significant problem for a substantial number of chronic kidney disease (CKD) patients which often goes unrecognized. The World Health Organization analgesic ladder and basic pharmacological principles can be used as a template for the assessment and treatment of pain in CKD patients. This review examines pain management principles for patients with CKD. | The prevalence and severity of symptoms in patients with advanced chronic kidney disease is higher than those of the general population and comparable to those with other chronic and serious medical conditions. Despite the prevalence and severity in this population, symptoms continue to be under-recognized and inadequately managed. The recognition of specific intradialytic pain syndromes such as pain related to arteriovenous access, headaches, muscle cramps or generalized pain by providers may aid in improving patient compliance and quality of life. The approach to pain management in end stage renal disease patients follows that of the general population with specific considerations regarding clearance and potential side effects guiding selection of agents. Overall, evidence is limited regarding the pharmacology of many medications in this population. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,789 |
BACKGROUND ::: Severe cutaneous burn causes transient mesenteric vasoconstriction and altered gut mucosal integrity. We recently showed that burn also increases gut epithelial cell death by apoptosis. The goal of this study was to determine whether changes in gut perfusion after burn contribute to burn-associated gut apoptosis. ::: ::: ::: STUDY DESIGN ::: We first correlated superior mesenteric artery blood flow with measurement of gut perfusion at the tissue level by laser doppler in four nonburned rats before, during, and after arterial clamping to validate our measurements of gut perfusion. We then characterized gut perfusion sequentially over time after burn; gut perfusion was measured 3 cm from the ligament of Treitz before burn and hourly for 6 hours. A group of control rats underwent the exact same protocol without the burn to exclude effects of anesthesia and laparotomy on tissue perfusion (n = 4). We studied a third group of rats with hypoperfusion of the same duration and magnitude induced mechanically without burn (n = 7). Sections of the proximal gut from all three groups (control without burn, burn, and hypoperfusion without burn) were examined for epithelial apoptosis. ::: ::: ::: RESULTS ::: Linear regression analysis demonstrated a strong correlation between superior mesenteric artery blood flow and intestinal tissue perfusion measured by laser doppler under both low and high flow conditions (r = 0.85). Laser doppler measurements of gut perfusion after burn showed deceased gut perfusion that was maximal at 2 hours postburn (p < 0.05), and that persisted for 4 hours (p < 0.05). By 6 hours, gut perfusion returned to baseline. Apoptosis increased significantly in the burn group (2.11 +/- 0.17%) compared with control (0.52 +/- 0.2%) and the mechanically decreased perfusion group (0.51 +/- .03) (p < 0.001). ::: ::: ::: CONCLUSIONS ::: We conclude that burn-induced gut hypoperfusion is insufficient to cause burn-related increased gut epithelial apoptosis. We speculate that the signal for increased gut epithelial apoptosis is primarily related to proinflammatory mediators induced by the burn wound. | Current definition of inflammation by its cardinal signs is obsolete and unsuitable for guiding adequate therapeutic strategies. Furthermore, present theory of the inflammatory process regarding vascular phenomena as essential for generation of cardinal signs is invalid and unable to explain well established empirical facts, particularly the extent of the osmotic pressure and temperature variations within the inflamed tissue. From five cardinal signs, there is actually just one specific macroscopic sign of inflammation, namely localized edema. Further, the driving force for tissue fluid accumulation is defined in biochemical terms and as such taken for the definition of the inflammatory process. Inflammation may be defined as a degenerative process which is intense enough to cause local accumulation of low molecular weight catabolic products, which in turn elevates tissue osmotic pressure that attracts extra fluid, with or without heat release sufficient for significant elevation of tissue temperature. This process is in a sharp contrast to the pathogenesis of burns, where externally applied heat causes a process that is in essence opposite to inflammation, bearing only some superficial similarities with the latter. The inflammatory process is itself a pathological process, whereas the natural anti-inflammatory response that ensues after acute inflammation tends to reverse tissue homeostasis towards normality and should therefore be regarded as a true defensive reaction of the affected tissue. Based on the therapeutic principle of reverse thermodynamics, heat application to the inflamed tissue is an obvious, yet non-exclusive therapeutic choice that follows from the given universal definition of inflammation. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,790 |
Objectives The aim of this study was to determine the association of visceral adiposity with severe outcomes in acute pancreatitis (AP). Methods This retrospective study included consecutive patients with AP admitted to a tertiary care hospital between January 2010 and January 2015 who underwent a computed tomography scan. The visceral adipose tissue (VAT) volume was estimated using the method of Linder and colleagues. Multivariable logistic regression analysis was conducted to assess VAT as a predictor of severe AP compared with other validated predictors of severity. Results Five hundred and seventy four patients were admitted during the study period, of which 252 had a computed tomography scan available. Patients with severe AP had a larger VAT area compared with those with mild or moderate AP (mean: 184.9 cm2 vs 79.9 cm2, P = 0.006). Patients who developed multisystem organ failure or had acute necrotic collections had a larger VAT area than those who did not (150.6 cm2 vs 91.0 cm2, P = 0.004 and 174.0 cm2 vs 91.9 cm2, P = 0.003, respectively). Visceral adipose tissue area demonstrated superior discrimination of severe AP compared with other severity predictors. Conclusions Increased VAT area is a strong predictor of severe pancreatitis, necrosis, and multisystem organ failure. | Background ::: Obesity plays an important role in acute pancreatitis. Assuming that the volume of visceral adipose tissue (VAT) directly influences the severity of acute pancreatitis, we investigated the relationship between VAT and acute pancreatitis. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,791 |
Vincristine has a high neurotoxicity level. If given intrathecally by accident, it can cause ascending radiculomyeloencephalopathy, which is almost always fatal. The authors report a rare case in which vincristine was accidentally injected intrathecally into a 32-year-old man. The patient, who had Burkitt lymphoma, was neurologically intact, and it is likely that his survival was made possible due to aggressive neurosurgical therapy. After immediate cerebrospinal fluid (CSF) aspiration, external ventricular and lumbar drains were placed for CSF irrigation, which was continued for 6 days. This CSF irrigation was combined with 1) the intrathecal administration of fresh-frozen plasma to bind the vincristine and 2) an intravenous antineurotoxic therapy involving pyridoxine, folic acid, and glutamic acid. The patient's first sensorimotor deficits occurred after 2 days, led to an incomplete sensorimotor dysfunction below T-9 within the next 17 days, but progressed no further. Supported by the scarce data culled from the reviewed literature, the authors hypothesize that prolonged CSF irrigation combined with antineurotoxic therapy contributed to the patient's satisfactory outcome. In conclusion, accidental intrathecal vincristine injection requires emergency and adequate neurosurgical therapy. | In a murine model system, folinic acid demonstrated host-protective properties during administration of repetitive and lethal doses of vincristine (VCR). Subsequently, folinic acid was evaluated in patients receiving VCR during an adjuvant chemotherapy program for stage II carcinoma of the breast. The toxicities, cumulative VCR dosage, and percentage of ideal dosage observed in 18 patients receiving folinic acid have been compared with those observed in 70 patients who previously received VCR without folinic acid in the same chemotherapy program. All patients ideally were intended to receive VCR 1.0 mg/m2 weekly for 6 weeks, with dose modification for neurotoxicity. Treatment patients received folinic acid 800 mg PO daily in three divided doses during the 6-week course. The degree of neurotoxic manifestations of VCR was similar in the treatment and comparison patients. Absent to mild neurotoxicity was observed in approximately 70% of patients in both groups; moderate or greater neurotoxicity occurred in about 30% of patients in both groups. Full dosage (6.0 mg/m2) was attained in 7 (39%) treatment patients and 17 (24%) comparison patients (P = 0.21). The mean percentage of the ideal dosage of VCR was 73.7 +/- 28.7 in patients receiving folinic acid and 76.1 +/- 20.5 in those given only VCR (P = 0.69). Hematologic toxicities were similar in both groups, but nausea occurred more frequently in the folinic acid group. Folinic acid in this dose and schedule afforded no protection from the neurotoxic side effects of VCR. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,792 |
Background Compliance is sometimes difficult for patients treated with temozolomide, because of the inconvenience due to the high daily number of capsules needed. Studies with other drugs showed that pillboxes increased patient satisfaction. Purpose To determine if pharmaceutical information and the use of pillboxes may improve satisfaction of patients treated with temozolomide. Materials and Methods This prospective and interventional study included adult patients who picked temozolomide up in our Hospital Pharmacy (01/03/2012 to 31/08/2012). In the first visit, patients previously treated with temozolomide completed a satisfaction questionnaire, which was adapted from the ESTAR questionnaire (ARPAS study). It consisted of 9 questions to be answered from 0 (very unsatisfied) to 6 (very satisfied), and another two items about temozolomide information. In addition, pharmaceutical information and pillboxes were provided to all patients. At their next visit, patients received another questionnaire, with 6 of the previous satisfaction questions and 5 new questions about usefulness of the pillbox and of the received information. Results 35 patients were evaluated with the first questionnaire (50.69 ± 13.38 years old; 77.14% were treated with ≥3 capsules per dose) and 28 of them filled in the second questionnaire (50.32 ± 12.45 years old; 75% taking ≥3 capsules per dose). 88.57% vs. 85.71% of patients took their pills in cycles of 5 days followed by 23 days without treatment. Satisfaction pre- and post-intervention was related to: the number of capsules prescribed per dose (4.43 ± 1.60 vs. 4.96 ± 0.84), the possibility of taking their treatment everywhere (5.17 ± 0.92 vs. 5.32 ± 0.82), and the convenience of the chemotherapeutic regime (5.06 ± 0.94 vs. 5.07 ± 1.05). The usefulness of the pharmaceutical attention, the pillbox and the leaflet were valuated as 5.46 ± 0.58, 5.39 ± 0.69 and 5.68 ± 0.48, respectively. Global satisfaction with pharmaceutical attention was 5.79 ± 0.42. Conclusions In this study, information provided by hospital pharmacist and the use of pillboxes improved satisfaction in patients treated with temozolomide. No conflict of interest. | The goal of this research was to observe which features, according to the users’ point of view, might influence the use of pillboxes. Older adults were surveyed in order to test different pillboxes and report their observations about their difficulties. Both the individuals and the pillboxes themselves have characteristics that might influence successful use, such as difficulty remembering medication names and lack of hand strength and the complexity of the pillboxes’ alarm system and opening mechanism. Pillboxes can be effective in helping older adults take their medication provided they are designed according to both dosage prescription and the user’s functional capacity. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,793 |
An activated renin-angiotensin system (RAS) within the central nervous system has been implicated in sympathoexcitation during various disease conditions including congestive heart failure (CHF). In particular, activation of the RAS in the paraventricular nucleus (PVN) of the hypothalamus has been recognized to augment sympathoexcitation in CHF. We observed a 2.6-fold increase in angiotensinogen (AGT) in the PVN of CHF. To elucidate the molecular mechanism for increased expression of AGT, we performed in silico analysis of the 3'-untranslated region (3'-UTR) of AGT and found a potential binding site for microRNA (miR)-133a. We hypothesized that decreased miR-133a might contribute to increased AGT in the PVN of CHF rats. Overexpression of miR-133a in NG108 cells resulted in 1.4- and 1.5-fold decreases in AGT and angiotensin type II (ANG II) type 1 receptor (AT1R) mRNA levels, respectively. A luciferase reporter assay performed on NG108 cells confirmed miR-133a binding to the 3'-UTR of AGT. Consistent with these in vitro data, we observed a 1.9-fold decrease in miR-133a expression with a concomitant increase in AGT and AT1R expression within the PVN of CHF rats. Furthermore, restoring the levels of miR-133a within the PVN of CHF rats with viral transduction resulted in a significant reduction of AGT (1.4-fold) and AT1R (1.5-fold) levels with a concomitant decrease in basal renal sympathetic nerve activity (RSNA). Restoration of miR-133a also abrogated the enhanced RSNA responses to microinjected ANG II within the PVN of CHF rats. These results reveal a novel and potentially unique role for miR-133a in the regulation of ANG II within the PVN of CHF rats, which may potentially contribute to the commonly observed sympathoexcitation in CHF.NEW & NOTEWORTHY Angiotensinogen (AGT) expression is upregulated in the paraventricular nucleus of the hypothalamus through posttranscriptional mechanism interceded by microRNA-133a in heart failure. Understanding the mechanism of increased expression of AGT in pathological conditions leading to increased sympathoexcitation may provide the basis for the possible development of new therapeutic agents with enhanced specificity. | The present study aimed to investigate the potential effects of growth differentiation factor 11 (GDF11) on isoproterenol (ISO)-induced heart failure (HF) and identify the underlying molecular mechanisms. A rat model of HF was induced in vivo by intraperitoneally administering ISO (5 mg/kg/day) for 7 days. After 4 weeks following establishment of the HF model, hemodynamic analysis demonstrated that ISO induced a significant increase in the left ventricular end-diastolic pressure and a decrease in the left ventricular systolic pressure and maximum contraction velocity. The plasma levels of myocardial injury markers, including lactate dehydrogenase (LDH), creatine kinase (CK), CK-muscle/brain which were determined using the corresponding assay kits and plasma brain natriuretic peptide which was detected by an ELISA kit, an important biomarker of HF, increased following ISO treatment. Furthermore, levels of GDF11 expression and protein, which were estimated using reverse transcription-quantitative polymerase chain reaction and an ELISA kit in plasma and western blotting in the heart tissue, respectively, significantly increased following ISO treatment. To demonstrate the effects of ISO on GDF11 production in cardiomyocytes, H9C2 cells (a cardiomyoblast cell line derived from embryonic rat heart tissue) were treated with ISO (50 nM) for 24 h in vitro; it was revealed that GDF11 protein and mRNA expression levels significantly increased following ISO treatment. In addition, recombinant GDF11 (rGDF11) administered to ISO-treated H9C2 cells resulted in decreased proliferation, which was detected via a CCK-8 assay, and increased LDH levels and cell apoptosis of cells, which was determined using Caspase-3 activity and Hoechst 33258 staining. Additionally, rGDF11 increased the levels of reactive oxygen species and malondialdehyde due to the upregulation of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) following rGDF11 treatment. Conversely, GDF11 knockdown reduced ISO-induced apoptosis by inhibiting oxidative stress injury. The results suggested that GDF11 production was upregulated in ISO-induced rats with HF and in ISO-treated H9C2 cells, and that rGDF11 treatment increased ISO-induced oxidative stress injury by upregulating Nox4 in H9C2 cells. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,794 |
BACKGROUND ::: Non-traumatic bone fractures in cancer patients are usually pathological fractures due to bone metastases. In head and neck cancer patients, clavicle stress fractures may occur as a result of atrophy of the trapezius muscle after neck dissection in which the accessory nerve becomes structurally or functionally damaged. ::: ::: ::: CASE REPORT ::: A 71-year-old man underwent modified radical neck dissection with accessory nerve preservation and post-operative radiotherapy for submandibular lymph node metastases of tongue cancer. Four weeks after the radiotherapy, a clavicle fracture, with osteomyelitis and abscess formation in the pectoralis major muscle, occurred. Unlike in simple stress fracture, long-term antibiotic administration and drainage surgery were required to suppress the inflammation. ::: ::: ::: CONCLUSION ::: As seen in the present patient, clavicle stress fractures may occur even after neck dissection in which the accessory nerve is preserved, and may be complicated by osteomyelitis and abscess formation owing to risk factors such as radiotherapy, tracheostomy and contiguous infection. | OBJECTIVE ::: The objective of this paper is to investigate the incidence rate, risk factors and outcome of osteomyelitis among patients with systemic lupus erythematosus (SLE). ::: ::: ::: MATERIALS AND METHODS ::: We conducted a cohort study using data for patients enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. Patients with SLE and age- and sex-matched controls without SLE were enrolled. Primary endpoint was the first occurrence of osteomyelitis. Risks of osteomyelitis in SLE patients were analyzed with Cox proportional hazards regression models, including age, sex, comorbidities and medications. ::: ::: ::: RESULTS ::: Among 24,705 SLE patients (88.4% women, mean age 35.8 years) with a median follow-up of 9.1 years, 386 patients had osteomyelitis. The incidence rate ratio (IRR) of osteomyelitis in the SLE group vs the control group was 8.52 (95% confidence interval (CI) 7.24-10.05). The SLE group had higher incidence rates of osteomyelitis than the control group, especially in pediatric subgroups (IRR 41.1 95% CI 18.57-107.35). Compared to controls, SLE patients experienced osteomyelitis at a younger age (42.3 vs 58.1 years) but did not have an increased risk of mortality (hazard ratio 0.7; 95% CI 0.21-2.38). Age >60 years, male gender, malignancy within five years, prior bone fracture and higher daily prednisolone dose (>7.5 mg) cumulatively for >180 days increased risk for osteomyelitis. ::: ::: ::: CONCLUSIONS ::: SLE patients have a higher IRR of osteomyelitis than controls. Pediatric and elder SLE patients, patients with a history of bone fracture, malignancy within five years and higher-dose glucocorticoid use have a higher risk of osteomyelitis and should be carefully monitored. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,795 |
Aims ::: We previously identified association between the ID3 SNP rs11574 and carotid intima-media thickness in the Diabetes Heart Study, a predominantly White diabetic population. The nonsynonymous SNP rs11574 results in an amino acid substitution in the C-terminal region of ID3, attenuating the dominant negative function of ID3 as an inhibitor of basic HLH factor E12-mediated transcription. In the current investigation, we characterize the association between the functionally significant polymorphism in ID3, rs11574, with human coronary pathology. ::: ::: ::: Methods and Results ::: The Multi-Ethnic Study of Atherosclerosis (MESA) is a longitudinal study of subclinical cardiovascular disease, including non-Hispanic White (n = 2,588), African American (n = 2,560) and Hispanic (n = 2,130) participants with data on coronary artery calcium (CAC). The Coronary Assessment in Virginia cohort (CAVA) included 71 patients aged 30–80 years, undergoing a medically necessary cardiac catheterization and intravascular ultrasound (IVUS) at the University of Virginia. ID3 SNP rs11574 risk allele was associated with the presence of CAC in MESA Whites (P = 0.017). In addition, the risk allele was associated with greater atheroma burden and stenosis in the CAVA cohort (P = 0.003, P = 0.04 respectively). The risk allele remained predictive of atheroma burden in multivariate analysis (Model 1: covariates age, gender, and LDL, regression coefficient = 9.578, SE = 3.657, p = 0.0110; Model 2: covariates Model 1, presence of hypertension, presence of diabetes, regression coefficient = 8.389, SE = 4.788, p = 0.0163). ::: ::: ::: Conclusions ::: We present additional cohorts that demonstrate association of ID3 SNP rs11574 directly with human coronary artery pathology as measured by CAC and IVUS: one a multiethnic, relatively healthy population with low levels of diabetes and the second a predominantly White population with a higher incidence of T2DM referred for cardiac catheterization. | Atherosclerosis is a progressive inflammatory disease of the medium to large arteries that is the largest contributor to cardiovascular disease. B-cell subsets have been shown in animal models of atherosclerosis to have both atherogenic and atheroprotective properties. In this review, we highlight the research that developed our understanding of the role of B cells in atherosclerosis both in humans and mice. From this we discuss the potential clinical impact B cells could have both as diagnostic biomarkers and as targets for immunotherapy. Finally, we recognize the inherent difficulty in translating findings from animal models into humans given the differences in both cardiovascular disease and the immune system between mice and humans, making the case for greater efforts at addressing the role of B cells in human atherosclerosis. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,796 |
Increases in vascular permeability and angiogenesis are crucial events to wound repair, tumoral growth and revascularization of tissues submitted to ischemia. An increased vascular permeability allows a variety of cytokines and growth factors to reach the damaged tissue. Nevertheless, the angiogenesis supply tissues with a wide variety of nutrients and is also important to metabolites clearance. It has been suggested that the natural latex from Hevea brasiliensis showed wound healing properties and angiogenic activity. Thus, the purpose of this work was to characterize its angiogenic activity and its effects on vascular permeability and wound healing. The serum fraction of the latex was separated from the rubber with reduction of the pH. The activity of the dialyzed serum fraction on the vascular permeability injected in subcutaneous tissue was assayed according Mile's method. The angiogenic activity was determined using a chick embryo chorioallantoic membrane assay and its effects on the wound-healing process was determined by the rabbit ear dermal ulcer model. The serum fraction showed evident angiogenic effect and it was effective in enhancing vascular permeability. In dermal ulcers, this material significantly accelerated wound healing. Moreover, the serum fraction boiled and treated with proteases lost these activities. These results are in accordance with the enhancement of wound healing observed in clinical trials carried out with a biomembrane prepared with the same natural latex. | Background:The prolonged tendon-healing process, the high costs associated with treatment, the increase in the number of injuries over the past decades, and the lack of consensus on the optimal tre... | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,797 |
To evaluate the clinical applications of serum thymidine kinase (TK) activity, we compared the results obtained with this parameter with those of other liver function tests in 27 patients with acute viral hepatitis and 16 normal controls. In those in the acute stage, the serum TK activity increased significantly to 55.5 +/- 66.5 U/L. There was no significant correlation between serum TK activity and findings for serum albumin, bilirubin, alkaline phosphatase or r-glutamyl transpeptidase. However, it did correlate significantly well with the serum activity of aspartate aminotransferase (AST) (r = 0.621, P < 0.01), alanine aminotransferase (ALT) (r = 0.551, P < 0.01), and lactate dehydrogenase (LDH) (r = 0.620, P < 0.01). Serum TK activity reached higher than 70 U/L in 8 of 11 patients with hepatitis A; however, no patients with the other types of hepatitis reached such a high level. During the recovery stage, the serum TK activity decreased significantly to 5.9 +/- 1.7 U/L (P < 0.01), and did not correlate with AST, ALT, LDH or other conventional liver function parameters. The data suggest that an elevation of serum TK in patients with acute viral hepatitis results from hepatocellular damage. A marked elevation of serum TK activity may thus provide a marker for acute hepatitis A infection. | The role of the vagus nerve in liver regeneration after partial hepatectomy was examined by comparing the effects of hepatic vagotomy (sectioning of the hepatic branch of the vagus nerve) with those of subdiaphragmatic vagotomy in rats. Hepatic vagotomy delayed but did not suppress the increase in the rate of hepatic DNA synthesis and the activity of thymidine kinase after partial hepatectomy. On the other hand, subdiaphragmatic vagotomy delayed and suppressed these indices. The time courses of restoration of liver DNA content after partial hepatectomy were not affected by hepatic vagotomy. However, this index was both delayed and suppressed in subdiaphragmatic vagotomized rats. Hepatic vagotomy did not affect the daily food intake or the body weight increase after partial hepatectomy. However, subdiaphragmatic vagotomy caused considerably more loss of food intake and body weight. There were no differences in the plasma insulin levels after partial hepatectomy among three groups. We concluded that a vagal specific effect is evident in the delay but fails to suppress liver regeneration. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,798 |
BACKGROUND ::: Local anesthetics are used to relieve pre- and postoperative pain, acting on both sodium channels and nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (NMJ). Bupivacaine acts as a non-competitive antagonist and has limitations, such as myotoxicity, neurotoxicity, and inflammation. Low-level laser therapy (LLLT) has anti-inflammatory, regenerative, and analgesic effects. The aim of the present study was to evaluate the effects of a gallium arsenide laser (GaAs) on the morphology of the NMJ and nAChRs after application of bupivacaine in the sternomastoid muscle. ::: ::: ::: METHODS ::: Thirty-two adult male Wistar rats received injections of bupivacaine 0.5% (Bupi: right antimere) and 0.9% sodium chloride (Cl: left antimere). Next, the animals were divided into a Control group (C) and a Laser group (LLLT). The laser group received LLLT (GaAs 904nm, 50mW, 4,8J) in both antimeres for five consecutive days. After seven days, the animals were euthanized and the surface portion of the sternomastoid muscle was removed, frozen, and subjected to morphological and morphometric analyses of the NMJs (nonspecific esterase reaction), confocal laser scanning, and an ultrastructural analysis. The nAChRs were quantified by Western blotting. ::: ::: ::: RESULTS ::: In the chloride group, the morphology and morphometry of the NMJs remained stable. The maximum diameters of the NMJs were lower in the Bupi (15.048±1.985) and LLLT/Bupi subgroups (15.456±1.983) compared to the Cl (18.502±2.058) and LLLT/Cl subgroups (19.356±2.522) (p<0.05). Ultrastructurally, LLLT reduced myonecrosis observed after application of bupivacaine, with recovery in the junctional folds and active zone. There was an increase in the perimeter of the LLLT/Bupi subgroup (150.33) compared to the Bupi subgroup (74.69) (p<0.01) observed by confocal microscopy. There was also an increase in the relative planar area of the NMJ after LBI (8.75) compared to CBupi (4.80) (p<0.01). An analysis of the protein expression of nAChRα1 showed no major differences in the groups studied. There was an increase in protein expression of the ε subunit after application of LLLT (13.055) compared to Bupi (0.251) (p<0.01). Taken together, the present experiments indicate that there was a positive association of the α and γ subunits (p<0.05). ::: ::: ::: CONCLUSIONS ::: These results demonstrate that LLLT at the dose used in this study reduced structural alterations in the NMJ and molecular changes in nAChRs triggered by bupivacaine, providing important data supporting the use of LLLT in therapeutic protocols for injuries triggered by local anesthetics. | The aim of this study was to determine the effects of gallium arsenide (GaAs) laser on IGF-I, MyoD, MAFbx, and TNF-α gene expression during the intermediate phase of muscle regeneration after cryoinjury 21 Wistar rats were divided into three groups (n = 7 per group): untreated with no injury (control group), cryoinjury without GaAs (injured group), and cryoinjury with GaAs (GaAs-injured group). The cryoinjury was induced in the central region of the tibialis anterior muscle (TA). The region injured was irradiated once a day during 14 days using GaAs laser (904 nm; spot size 0.035 cm2, output power 50 mW; energy density 69 J cm−2; exposure time 4 s per point; final energy 4.8 J). Twenty-four hours after the last application, the right and left TA muscles were collected for histological (collagen content) and molecular (gene expression of IGF-I, MyoD, MAFbx, and TNF-α) analyses, respectively. Data were analyzed using one-way ANOVA at P < 0.05. There were no significant (P > 0.05) differences in collagen density and IGF-I gene expression in all experimental groups. There were similar (P < 0.05) decreases in MAFbx and TNF-α gene expression in the injured and GaAs-injured groups, compared to control group. The MyoD gene expression increased (P = 0.008) in the GaAs-injured group, but not in the injured group (P = 0.338), compared to control group. GaAs laser therapy had a positive effect on MyoD gene expression, but not IGF-I, MAFbx, and TNF-α, during intermediary phases (14 days post-injury) of muscle repair. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,799 |
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